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  • 101.
    Bergman, Hilde-Marlene
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lindfors, Lina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Lanekoff, Ingela
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Metabolite aberrations at early onset of diabetes detected in rat kidney using mass spectrometry imaging2019Inngår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 411, nr 13, s. 2809-2816Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes.

  • 102.
    Bergman, Hilde-Marléne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Applications of nanospray desorption electrospray ionization mass spectrome: Analysis of lipids and metabolites in brain tissue sections and single cells2016Licentiatavhandling, med artikler (Annet vitenskapelig)
    Delarbeid
    1. Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization
    Åpne denne publikasjonen i ny fane eller vindu >>Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization
    2016 (engelsk)Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, nr 12, s. 3686-3695Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Small molecule neurotransmitters are essential for the function of the nervous system, and neurotransmitter imbalances are often connected to neurological disorders. The ability to quantify such imbalances is important to provide insights into the biochemical mechanisms underlying the disorder. This proof-of-principle study presents online quantification of small molecule neurotransmitters, specifically acetylcholine, γ-aminobutyric acid (GABA) and glutamate, in rat brain tissue sections using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging. By incorporating deuterated internal standards in the nano-DESI solvent we show identification, accurate mapping, and quantification of these small neurotransmitters in rat brain tissue without introducing any additional sample preparation steps. We find that GABA is about twice as abundant in the medial septum-diagonal band complex (MSDB) as in the cortex, while glutamate is about twice as abundant in the cortex as compared to the MSDB. The study shows that nano-DESI is well suited for imaging of small molecule neurotransmitters in health and disease.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-281314 (URN)10.1039/c5an02620b (DOI)000378942900021 ()26859000 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, VR 621-2013-4231Swedish Foundation for Strategic Research , SSF ICA-6
    Tilgjengelig fra: 2016-03-22 Laget: 2016-03-22 Sist oppdatert: 2018-11-29
    2. Detection of endogenous lipids and metabolites in single cells using nano-DESI
    Åpne denne publikasjonen i ny fane eller vindu >>Detection of endogenous lipids and metabolites in single cells using nano-DESI
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-291338 (URN)
    Tilgjengelig fra: 2016-05-01 Laget: 2016-05-01 Sist oppdatert: 2018-11-29
  • 103.
    Bergman, Hilde-Marléne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Applications of nanospray desorption electrospray ionization mass spectrometry: In situ lipid and metabolite analysis from cells to tissue2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Ambient mass spectrometry (MS) has proved to be an important addition to the bioanalytical toolbox. These methods perform analyte sampling and ionization under atmospheric pressure, and require very little sample preparation other than the sampling process in front of the machine. Nanospray desorption electrospray ionization (nano-DESI) is an ambient MS technique developed in 2010 that utilizes localized liquid extraction for surface sampling. The aim of this thesis was to explore the possibilities of this technique, and identify areas in which nano-DESI MS could further contribute to the community of MS-based surface analysis.

    One such area was found to be mass spectrometry imaging (MSI) of small-molecule neurotransmitters. By the use of deuterated standards of acetylcholine, γ-aminobutyric acid and glutamate, the respective endogenous compounds were successfully imaged in coronal sections of rat brain. The use of internal standards was shown to be essential to compensatee for matrix effects in different regions of the brain. In a second imaging study, nano-DESI MSI was used to compare the chemical profiles of diabetic rat kidney tissue and control. Analysis was performed on kidney two weeks after diabetic onset, before any pathohistological changes relating to diabetic nephropathy can be seen in a microscope. In our study, it was shown that a large number of chemical species related to energy metabolism were detected with altered signal intensity in diabetic kidney tissue.

    To push the limits of nano-DESI analysis, its use for single-cell analysis was evaluated. By placing buccal epithelial cells in contact with the nano-DESI probe, it was possible to identify 46 endogenous compounds and detect differences between cells from three human donors. In addition, it was shown that molecules from single cells on a surface could be detected by scanning the surface with the nano-DESI probe, which opens up for development of an automated analysis with higher throughput.

    The last study in this thesis was concerned with method development rather than application, as it presented a setup for pneumatically assisted nano-DESI. Evaluation showed that the setup provided improved sensitivity in the analysis of small metabolites, and provided the possibility of using pure water as nano-DESI solvent.

    Delarbeid
    1. Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization
    Åpne denne publikasjonen i ny fane eller vindu >>Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization
    2016 (engelsk)Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, nr 12, s. 3686-3695Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Small molecule neurotransmitters are essential for the function of the nervous system, and neurotransmitter imbalances are often connected to neurological disorders. The ability to quantify such imbalances is important to provide insights into the biochemical mechanisms underlying the disorder. This proof-of-principle study presents online quantification of small molecule neurotransmitters, specifically acetylcholine, γ-aminobutyric acid (GABA) and glutamate, in rat brain tissue sections using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging. By incorporating deuterated internal standards in the nano-DESI solvent we show identification, accurate mapping, and quantification of these small neurotransmitters in rat brain tissue without introducing any additional sample preparation steps. We find that GABA is about twice as abundant in the medial septum-diagonal band complex (MSDB) as in the cortex, while glutamate is about twice as abundant in the cortex as compared to the MSDB. The study shows that nano-DESI is well suited for imaging of small molecule neurotransmitters in health and disease.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-281314 (URN)10.1039/c5an02620b (DOI)000378942900021 ()26859000 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, VR 621-2013-4231Swedish Foundation for Strategic Research , SSF ICA-6
    Tilgjengelig fra: 2016-03-22 Laget: 2016-03-22 Sist oppdatert: 2018-11-29
    2. Metabolite aberrations at early onset of diabetes detected in rat kidney using mass spectrometry imaging
    Åpne denne publikasjonen i ny fane eller vindu >>Metabolite aberrations at early onset of diabetes detected in rat kidney using mass spectrometry imaging
    Vise andre…
    2019 (engelsk)Inngår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 411, nr 13, s. 2809-2816Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes.

    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot analytisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-347672 (URN)10.1007/s00216-019-01721-5 (DOI)000468133600008 ()30895347 (PubMedID)
    Forskningsfinansiär
    Swedish Foundation for Strategic Research Swedish Research CouncilSwedish Diabetes AssociationAstraZeneca
    Merknad

    Title in dissertation list of papers: Metabolite aberrations at early onset of diabetes detected in rat kidney using mass spectrometry imaging

    Tilgjengelig fra: 2018-04-05 Laget: 2018-04-05 Sist oppdatert: 2019-06-19bibliografisk kontrollert
    3. Profiling and quantifying endogenous molecules in single cells using nano-DESI MS
    Åpne denne publikasjonen i ny fane eller vindu >>Profiling and quantifying endogenous molecules in single cells using nano-DESI MS
    2017 (engelsk)Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 142, nr 19, s. 3639-3647Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Molecular profiling of single cells has the potential to significantly advance our understanding of cell function and cellular processes of importance to health and disease. In particular, small molecules with rapid turn-over rates can reveal activated metabolic pathways resulting from an altered chemical environment or cellular events such as differentiation. Consequently, techniques for quantitative metabolite detection acquired in a higher throughput manner are needed to characterize the biological variability between seemingly homogenous cells. Here, we show that nanospray desorption electrospray ionization (nano-DESI) mass spectrometry ( MS) enables sensitive molecular profiling and quantification of endogenous species in single cells in a higher throughput manner. Specifically, we show a large number of detected amino acids and phospholipids, including plasmalogens, readily detected from single cheek cells. Further, by incorporating a phosphatidylcholine ( PC) internal standard into the nano-DESI solvent, we determined the total amount of PC in one cell to be 1.2 pmoles. Finally, we describe a higher throughput approach where molecules in single cells are automatically profiled. These developments in single cell analysis provide a basis for future studies to understand cellular processes related to drug effects, cell differentiation and altered chemical microenvironments.

    sted, utgiver, år, opplag, sider
    ROYAL SOC CHEMISTRY, 2017
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot analytisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-336430 (URN)10.1039/c7an00885f (DOI)000411703800013 ()28835951 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, VR 621-2013-4231Swedish Foundation for Strategic Research , SSF ICA-6
    Tilgjengelig fra: 2017-12-15 Laget: 2017-12-15 Sist oppdatert: 2018-11-29
    4. A pneumatically assisted nanospray desorption electrospray ionization source for increased solvent versatility and enhanced metabolite detection from tissue
    Åpne denne publikasjonen i ny fane eller vindu >>A pneumatically assisted nanospray desorption electrospray ionization source for increased solvent versatility and enhanced metabolite detection from tissue
    2017 (engelsk)Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 142, nr 18, s. 3424-3431Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Nanospray desorption electrospray ionization (nano-DESI) has been established as a powerful technique for mass spectrometry imaging (MSI) of biomolecules from tissue samples. The direct liquid extraction of analytes from a surface at ambient pressure negates the need for significant sample preparation or matrix application. Although many recent studies have applied nano-DESI to new and exciting applications, there has not been much work in the development and improvement of the nano-DESI source. Here, we incorporate a nebulizer to replace the self-aspirating secondary capillary in the conventional nano-DESI setup, and characterize the device by use of rat kidney tissue sections. We find that the pneumatically assisted nano-DESI device offers improved sensitivity for metabolite species by 1-3 orders of magnitude through more complete desolvation and reduced ionization suppression. Further, the pneumatically assisted nano-DESI device reduces the dependence on probe-to-surface distance and enables sampling and imaging using pure water as the nano-DESI solvent. This provides exclusive detection and imaging of many highly polar endogenous species. Overall, the developed pneumatically assisted nano-DESI device provides more versatile solvent selection and an increased sensitivity for metabolites, which generates ion images of higher contrast - allowing for more intricate studies of metabolite distribution.

    sted, utgiver, år, opplag, sider
    ROYAL SOC CHEMISTRY, 2017
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-334756 (URN)10.1039/c7an00901a (DOI)000409919200016 ()28828451 (PubMedID)
    Forskningsfinansiär
    Swedish Foundation for Strategic Research , SSF ICA-6Swedish Research Council, VR 621-2013-4231
    Tilgjengelig fra: 2017-11-27 Laget: 2017-11-27 Sist oppdatert: 2018-11-29
  • 104. Bergman, Hilde-Marléne
    et al.
    Andersson, Ingela
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Detection of endogenous lipids and metabolites in single cells using nano-DESIManuskript (preprint) (Annet vitenskapelig)
  • 105.
    Bergman, Hilde-Marléne
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lundin, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Andersson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Lanekoff, Ingela
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization2016Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, nr 12, s. 3686-3695Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Small molecule neurotransmitters are essential for the function of the nervous system, and neurotransmitter imbalances are often connected to neurological disorders. The ability to quantify such imbalances is important to provide insights into the biochemical mechanisms underlying the disorder. This proof-of-principle study presents online quantification of small molecule neurotransmitters, specifically acetylcholine, γ-aminobutyric acid (GABA) and glutamate, in rat brain tissue sections using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging. By incorporating deuterated internal standards in the nano-DESI solvent we show identification, accurate mapping, and quantification of these small neurotransmitters in rat brain tissue without introducing any additional sample preparation steps. We find that GABA is about twice as abundant in the medial septum-diagonal band complex (MSDB) as in the cortex, while glutamate is about twice as abundant in the cortex as compared to the MSDB. The study shows that nano-DESI is well suited for imaging of small molecule neurotransmitters in health and disease.

  • 106.
    Bergman, Nina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingvar Eidhammer, Harald Barsnes, Geir Egil Eide, and Lennart Martens:: Computational and statistical methods for protein quantification by mass spectrometry2014Inngår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, nr 6, s. 1575-1576Artikkel, omtale (Fagfellevurdert)
  • 107.
    Bergman, Nina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Recent developments in proteomic methods and disease biomarkers2014Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 139, s. 3836-3851Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Proteomic methodologies for identification and analysis of biomarkers have gained more attention during recent years and have evolved rapidly. Identification and detection of disease biomarkers are important to foresee outbreaks of certain diseases thereby avoiding surgery and other invasive and expensive medical treatments for patients. Thus, more research into discovering new biomarkers and new methods for faster and more accurate detection is needed. It is often difficult to detect and measure biomarkers because of their low concentrations and the complexity of their respective matrices. Therefore it is hard to find and validate methods for accurate screening methods suitable for clinical use. The most recent developments during the last three years and also some historical considerations of proteomic methodologies for identification and validation of disease biomarkers are presented in this review.

  • 108.
    Bergman, Nina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Shevchenko, Denys
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Approaches for the analysis of low molecular weight compounds with laser desorption/ionization techniques and mass spectrometry2014Inngår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, nr 1, s. 49-61Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    This review summarizes various approaches for the analysis of low molecular weight (LMW) compounds by different laser desorption/ionization mass spectrometry techniques (LDI-MS). It is common to use an agent to assist the ionization, and small molecules are normally difficult to analyze by, e.g., matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) using the common matrices available today, because the latter are generally small organic compounds themselves. This often results in severe suppression of analyte peaks, or interference of the matrix and analyte signals in the low mass region. However, intrinsic properties of several LDI techniques such as high sensitivity, low sample consumption, high tolerance towards salts and solid particles, and rapid analysis have stimulated scientists to develop methods to circumvent matrix-related issues in the analysis of LMW molecules. Recent developments within this field as well as historical considerations and future prospects are presented in this review.

  • 109.
    Bergman, Nina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Thapper, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Styring, Stenbjorn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Shevchenko, Denys
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Quantitative determination of the Ru(bpy)(3)(2+) cation in photochemical reactions by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry2014Inngår i: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 6, nr 21, s. 8513-8518Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The coordination compound of Ru(II) with three 2,2'-bipyridine ligands possesses a potent photosensitization capacity for electron- and energy-transfer processes. In combination with salts of peroxydisulfate acid as sacrificial electron acceptors, Ru(bpy)(3)(2+) is widely used for photocatalytic oxidative transformations in organic synthesis and water splitting. The drawback of this system is that bipyridine degrades under the resulting strongly oxidative conditions, the concentration of Ru(bpy)(3)(2+) diminishes, and the photocatalytic reaction eventually stops. A commonly employed assay for the determination of Ru(bpy)(3)(2+), UV-Vis spectroscopy, has low selectivity and does not distinguish between the intact complex and its decayed forms. Here, we report a matrix assisted laser desorption/ionisation mass spectrometric method for the quantitative analysis of Ru(bpy)(3)(2+) in photochemical reaction mixtures. The developed method was successfully used for the determination of intact Ru(bpy)(3)(2+) during the course of the water photooxidation reaction. The significant difference between the results of MALDI MS and UV-Vis analyses was observed.

  • 110.
    Bergman, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Hall, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Rahman, Rashidur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Blomgren, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Larhed, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Svedberg, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Thibblin, Alf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Wångsell, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Synthesis and Labelling of a Piperazine-Based Library of 11C-Labeled Ligands for Imaging of the Vesicular Acetylcholine Transporter2014Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 57, nr 8, s. 525-532Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cholinergic system is involved in neurodegenerative diseases, and visualization of cholinergic innervations with positron emission tomography (PET) would be a useful tool in understanding these diseases. A ligand for the vesicular acetylcholine transporter (VAChT), acknowledged as a marker for cholinergic neurons, could serve as such a PET tracer. The aim was to find a VAChT PET tracer using a library concept to create a small but diverse library of labeled compounds. From the same precursor and commercially available aryl iodides 6a-f, six potential VAChT PET tracers, [C-11]-(+/-)5a-f, were C-11-labeled by a palladium (0)-mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [C-11]-(+/-)5a-f were obtained in radiochemical purities >95% with decay-corrected radiochemical yields and specific radioactivities between 4-25% and 124-597 GBq/mu mol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [C-11]-(+/-)5d and [C-11]-(+/-)5e showed specific binding but not enough to permit further preclinical studies. To conclude, a general method for a facile synthesis and labeling of a small piperazine-based library of potential PET tracers for imaging of VAChT was shown, and in upcoming work, another scaffold will be explored using this approach.

  • 111.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Leveraging the power of mass spectrometry to unravel complex brain pathologies2019Inngår i: CLINICAL MASS SPECTROMETRY, ISSN 2376-9998, Vol. 14, s. 63-65Artikkel i tidsskrift (Annet vitenskapelig)
  • 112.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Proteomics to Understand the Degenerative Matter2014Inngår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 75, s. S10-S10Artikkel i tidsskrift (Annet vitenskapelig)
  • 113.
    Bergquist, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Baykut, Gökhan
    Bruker Daltonik GmbH, 28359 Bremen, Germany.
    Bergquist, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Witt, Matthias
    Bruker Daltonik GmbH, 28359 Bremen, Germany.
    Mayer, Franz-Josef
    Bruker Daltonik GmbH, 28359 Bremen, Germany.
    Baykut, Doan
    Institute of Biophysics, University of Frankfurt, 60438 Frankfurt/M, Germany.
    Human Myocardial Protein Pattern Reveals Cardiac Diseases2012Inngår i: International Journal of Proteomics, ISSN 2090-2174, Vol. 2012, s. 342659-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Proteomic profiles of myocardial tissue in two different etiologies of heart failure were investigated using high performance liquid chromatography (HPLC)/Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Right atrial appendages from 10 patients with hemodynamically significant isolated aortic valve disease and from 10 patients with isolated symptomatic coronary heart disease were collected during elective cardiac surgery. As presented in an earlier study by our group (Baykut et al., 2006), both disease forms showed clearly different pattern distribution characteristics. Interesting enough, the classification patterns could be used for correctly sorting unknown test samples in their correct categories. However, in order to fully exploit and also validate these findings there is a definite need for unambiguous identification of the differences between different etiologies at molecular level. In this study, samples representative for the aortic valve disease and coronary heart disease were prepared, tryptically digested, and analyzed using an FT-ICR MS that allowed collision-induced dissociation (CID) of selected classifier masses. By using the fragment spectra, proteins were identified by database searches. For comparison and further validation, classifier masses were also fragmented and analyzed using HPLC-/Matrix-assisted laser desorption ionization (MALDI) time-offlight/time-of-flight (TOF/TOF) mass spectrometry. Desmin and lumican precursor were examples of proteins found in aortic samples at higher abundances than in coronary samples. Similarly, adenylate kinase isoenzyme was found in coronary samples at a higher abundance. The described methodology could also be feasible in search for specific biomarkers in plasma or serum for diagnostic purposes.

  • 114.
    Bergquist, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Turner, Charlotta
    Lund Univ, Dept Chem, Ctr Anal & Synth, Lund, Sweden..
    Analytical chemistry for a sustainable society - trends and implications2018Inngår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 410, nr 14, s. 3235-3237Artikkel i tidsskrift (Annet vitenskapelig)
  • 115.
    Bergquist, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Huss, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Hästbacka, Johanna
    Lindholm, Catharina
    Martijn, Cecile
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Rylander, Christian
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Glucocorticoid receptor expression and binding capacity in patients with burn injury2016Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, nr 2, s. 213-221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.

    Methods

    Blood was sampled from 13 patients on admission and days 7, 14 and 21, and once from 16 healthy subjects. Patients were grouped according to the extent of burn and to any sepsis on day 7. Expression and binding capacity of GR were determined as arbitrary units using flow cytometry.

    Results

    GR expression and binding capacity were increased compared to healthy subjects in most circulating leucocyte subsets on admission irrespective of burn size. Patients with sepsis on day 7 displayed increased GR expression in T lymphocytes (51.8%, < 0.01) compared to admission. There was a negative correlation between GR binding capacity in neutrophils and burn size after 14 days (< 0.05).

    Conclusions

    GR expression and binding capacity are increased in most types of circulating leucocytes of severely burned patients on their admission to specialized burn care. If sepsis is present after 1 week, it is associated with higher GR expression in T lymphocytes and NK cells.

  • 116.
    Bergsaker, H.
    et al.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England.;KTH Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, SE-10405 Stockholm, Sweden..
    Bykov, I.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England.;KTH Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, SE-10405 Stockholm, Sweden..
    Zhou, Y.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England.;KTH Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, SE-10405 Stockholm, Sweden..
    Petersson, P.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England.;KTH Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, SE-10405 Stockholm, Sweden..
    Possnert, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, För teknisk-naturvetenskapliga fakulteten gemensamma enheter, Tandemlaboratoriet. EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England..
    Likonen, J.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England.;VTT Tech Res Ctr Finland, POB 1000, FI-02044 Espoo, Finland..
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England..
    Koivuranta, S.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England.;VTT Tech Res Ctr Finland, POB 1000, FI-02044 Espoo, Finland..
    Widdowson, A. M.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England.;CCFE, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England..
    Deep deuterium retention and Be/W mixing at tungsten coated surfaces in the JET divertor2016Inngår i: Physica Scripta, ISSN 0031-8949, E-ISSN 1402-4896, Vol. T167, artikkel-id 014061Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Surface samples from a full poloidal set of divertor tiles exposed in JET through operations 2010-2012 with ITER-like wall have been investigated using SEM, SIMS, ICP-AES analysis and micro beam nuclear reaction analysis (mu-NRA). Deposition of Be and retention of D is microscopically inhomogeneous. With careful overlaying of mu-NRA elemental maps with SEM images, it is possible to separate surface roughness effects from depth profiles at microscopically flat surface regions, without pits. With (He-3, p) mu-NRA at 3-5 MeV beam energy the accessible depth for D analysis in W is about 9 mu m, sufficient to access the W/Mo and Mo/W interfaces in the coatings and beyond, while for Be in W it is about 6 mu m. In these conditions, at all plasma wetted surfaces, D was found throughout the whole accessible depth at concentrations in the range 0.2-0.7 at% in W. Deuterium was found to be preferentially trapped at the W/Mo and Mo/W interfaces. Comparison is made with SIMS profiling, which also shows significant D trapping at the W/Mo interface. Mixing of Be and W occurs mainly in deposited layers.

  • 117.
    Bergstrand, Nill
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Fysikalisk-kemiska institutionen.
    Bohl, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Carlsson, Jörgen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Fysikalisk-kemiska institutionen.
    Ghaneolhosseine, Hadi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Fysikalisk-kemiska institutionen.
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Jonsson, Markus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Fysikalisk-kemiska institutionen.
    Silvander, Mats
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Fysikalisk-kemiska institutionen.
    Sjöberg, Stefan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Stabilised Liposomes with Double Targeting for Use in BNCT2000Inngår i: Contemporary Boron Chemistry / [ed] Matthew Davidson, Cambridge, UK: Royal Society of Chemistry, 2000, s. 131-134Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 118.
    Bergström, L. Magnus
    et al.
    Department of Chemistry, Surface, and Corrosion Science, School of Chemical Science and Engineering, KTH Royal Institute of Technology, SE-10044 Stockholm, Sweden.
    Skoglund, Sara
    Department of Chemistry, Surface, and Corrosion Science, School of Chemical Science and Engineering, KTH Royal Institute of Technology, SE-10044 Stockholm, Sweden.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Grillo, Isabelle
    Institut Laue Langevin, DS/LSS, 6 rue Jules Horowitz, BP156, 38042 Grenoble Cedex 9, France.
    Self-Assembly in Mixtures of an Anionic and a Cationic Surfactant: A Comparison between Small-Angle Neutron Scattering and Cryo-Transmission Electron Microscopy2013Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 29, nr 38, s. 11834-11848Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The self-assembly in SOS-rich mixtures of the anionic surfactant sodium octyl sulfate (SOS) and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) has been investigated with the complementary techniques small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). Both techniques confirm the simultaneous presence of open and closed bilayer structures in highly diluted samples as well as the existence of small globular and large elongated micelles at higher concentrations. However, the two techniques sometimes differ with respect to which type of aggregates is present in a particular sample. In particular, globular or wormlike micelles are sometimes observed with cryo-TEM in the vicinity of the micelle-to-bilayer transition, although only bilayers are present according to SANS and the samples appear bluish to the eye. A similar discrepancy has previously been reported but could not be satisfactorily rationalized. On the basis of our comparison between in situ (SANS) and ex situ (cryo-TEM) experimental techniques, we suggest that this discrepancy appears mainly as a result of the non-negligible amount of surfactant adsorbed at interfaces of the thin sample film created during the cryo-TEM specimen preparation. Moreover, from our detailed SANS data analysis, we are able to observe the unusually high amount of free surfactant monomers present in SOS-rich mixtures of SOS and CTAB, and the experimental results give excellent agreement with model calculations based on the Poisson?Boltzmann mean field theory. Our careful comparison between model calculations and experiments has enabled us to rationalize the dramatic microstructural transformations frequently observed upon simply diluting mixtures of an anionic and a cationic surfactant.

  • 119.
    Bergström, L. Magnus
    et al.
    School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, KTH Royal Institute of Technology, Sweden.
    Skoglund, Sara
    School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, KTH Royal Institute of Technology, Sweden.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Grillo, Isabelle
    Institut Laue Langevin, DS/LSS, 6 rue Jules Horowitz, B.P. 156, 38042 Grenoble Cedex 9, France.
    Spontaneous Transformations between Surfactant Bilayers of Different Topologies Observed in Mixtures of Sodium Octyl Sulfate and Hexadecyltrimethylammonium Bromide2014Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 30, nr 14, s. 3928-3938Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The influence of adding salt on the self-assembly in sodium octyl sulfate (SOS)-rich mixtures of the anionic surfactant SOS and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) have been investigated with the two complementary techniques, small-angle neutron scattering (SANS) and cryo-transmission electron microscopy. We are able to conclude that addition of a substantial amount of inert salt, NaBr, mainly has three effects on the structural behaviors: (i) the micelles become much larger at the transition from micelles to bilayers, (ii) the fraction of bilayer disks increases at the expense of vesicles, and (iii) bilayer aggregates perforated with holes are formed in the most diluted samples. A novel form factor valid for perforated bilayer vesicles and disks is introduced for the first time and, as a result, we are able to directly observe the presence of perforated bilayers by means of fitting SANS data with an appropriate model. Moreover, we are able to conclude that the morphology of bilayer aggregates changes according to the following sequence of different bilayer topologies, vesicles ? disks ? perforated bilayers, as the electrolyte concentration is increased and surfactant mole fraction in the bilayer aggregates approaches equimolarity. We are able to rationalize this sequence of transitions as a result of a monotonous increase of the bilayer saddle-splay constant (k?cbi) with decreasing influence from electrostatics, in agreement with theoretical predictions as deduced from the Poisson?Boltzmann theory.

  • 120.
    Bergström Lind, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Artemenko, Konstantin A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Elfineh, Lioudmila
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zhao, Yanhong
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    The phosphoproteome of the adenovirus type 2 virion2012Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 433, nr 1, s. 253-261Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have used a proteomics approach to identify sites of phosphorylation in the structural proteins of the Adenovirus type 2 particle. This protein modification might play an important role during infection. Peptides from highly purified virus were enriched for phosphorylations and analyzed by liquid chromatography-high-resolving mass spectrometry. Phosphorylations were identified in 11 structural peptides and 29 non-redundant phosphorylation sites were unambiguously assigned to specific amino acid. An unexpected result was the finding of phosphotyrosine in two of the viral polypeptides. The most highly phosphorylated protein was pIIIa with 12 identified phosphorylation sites. An identified preference for proline or leucine residue flanking the phosphorylation sites downstream suggests that cellular kinases are involved in many of the phosphorylations. Structural modeling showed that one site in the hexon is located on the outer side of the virus and could be of importance for the virus when attaching and entering cells.

  • 121.
    Bergström Lind, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Artemenko, Konstantin A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    A strategy for identification of protein tyrosine phosphorylation2012Inngår i: Methods, ISSN 1046-2023, E-ISSN 1095-9130, Vol. 56, nr 2, s. 275-283Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To develop methods for studying phosphorylation of protein tyrosine residues is an important task since this protein modification regulates many cellular functions and often is involved in oncogenesis. An optimal protocol includes enrichment of tyrosine phosphorylated (pTyr) peptides or proteins, followed by a high resolving analytical method for identification of the enriched components. In this Methods paper, we describe a working strategy on how immunoaffinity enrichments, using anti-pTyr antibodies, combined with mass spectrometric (MS) analysis can be used to study the pTyr proteome. We describe in detail how our procedure was used to characterize the pTyr proteome of K562 leukemia cells. Important questions concerning the use of different anti-pTyr antibodies, enrichments performed at the peptide and/or the protein level, pooling of enrichments and requirements for the MS characterization are discussed.

  • 122. Bergvall, Ulrika A.
    et al.
    Co, Michelle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Bergstrom, Roger
    Sjöberg, Per J. R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Waldebäck, Monica
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Turner, Charlotta
    Anti-browsing effects of birch bark extract on fallow deer2013Inngår i: European Journal of Forest Research, ISSN 1612-4669, E-ISSN 1612-4677, Vol. 132, nr 5-6, s. 717-725Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A major problem within forest industry is unwanted browsing on seedlings from mammalian herbivores. The aim of this study was to evaluate the effects of birch bark extracts as repellents towards fallow deer. Birch bark was extracted in a conventional way with ethanol as solvent at ambient temperature and with a new method, liquid CO2 extraction. An analysis of the ethanol-extracted birch bark showed that it contained large amounts of terpenoids, of which the most abundant was betulin. In seven different treatment trials, we used 15 individually handled fallow deer. To investigate the binary taste preferences, birch bark extract was added to food and presented in two bowls in typical two-choice tests. We found that the amount of a food type consumed during a trial and the number of shifts between food bowls were dependent on the amount of the birch extract the food contained. Concentrations of above 1 % by dry weight of birch extract acted as a repellent. In addition, such concentrations produced shorter feeding bouts by a greater willingness to change bowls. Therefore, our conclusion is that birch bark extract acts as a repellent towards fallow deer and is therefore likely to act as a repellent against other deer species. In addition, we show that birch bark extract produced by the new and more environmentally sustainable method employing liquid CO2 mixed with ethanol has the same repellent effect as the traditional ethanol extraction.

  • 123.
    Berndtson, Emma
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Qualitative analysis of LGD-4033 and its metabolites in equine plasma using UHPLC-MS(MS) for doping control purposes2017Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    A new class of drugs has been developed for treatment of muscle and bone mass wasting diseases called non-steroidal selective androgen receptor modulators (SARMs). Because of their positive androgenic effects such as muscle gain, they are desirable as performance enhancers.

    One of those substances is LGD-4033 (4-[(2R)-2-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)- benzonitrile). It has been detected in human samples in routine doping control and another SARM has been detected in an equine blood sample in routine doping control. It is therefore indicated that SARMs need to be screened for in routine testing in equestrian sport.

    The aim of this project was to identify what metabolites were found in equine plasma after an intra venous administration of LGD-4033 using UHPLC coupled with QToF-MS and determine whether the parent compound or any of its metabolites were most suitable for doping control.

    With the sample preparation method protein precipitation, six possible metabolites were identified in samples from three horses. Two of the metabolites were identified as phase I-metabolites (monohydroxylated and dihydroxylated). Four of the metabolites were identified as phase II-metabolites, where glucuronidation had occurred.

    The most suitable species for doping control were determined based on a semi- quantification and were M1a, M2 and M3a. 

  • 124.
    Berrier, Audrey
    et al.
    Universität Stuttgart, Physikalisches Institut, Germany.
    Schaafsma, Martijn C.
    FOM Institute AMOLF, Centre for Nanophotonics, c/o Philips Research Laboratories, Eindhoven, Netherlands.
    Nonglaton, Guillaume
    CEA Leti, MINATEC Campus, Department of microtechnologies for Biology and Healthcare, France.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Rivas, Jaime Gómez
    FOM Institute AMOLF, Centre for Nanophotonics, c/o Philips Research Laboratories AND COBRA Research Institute, Eindhoven University of Technology, Netherlands .
    Selective detection of bacterial layers with terahertz plasmonic antennas2012Inngår i: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 3, nr 11, s. 2937-2949Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Current detection and identification of micro-organisms is based on either rather unspecific rapid microscopy or on more accurate complex, time-consuming procedures. In a medical context, the determination of the bacteria Gram type is of significant interest. The diagnostic of microbial infection often requires the identification of the microbiological agent responsible for the infection, or at least the identification of its family (Gram type), in a matter of minutes. In this work, we propose to use terahertz frequency range antennas for the enhanced selective detection of bacteria types. Several microorganisms are investigated by terahertz time-domain spectroscopy: a fast, contactless and damage-free investigation method to gain information on the presence and the nature of the microorganisms. We demonstrate that plasmonic antennas enhance the detection sensitivity for bacterial layers and allow the selective recognition of the Gram type of the bacteria.

  • 125.
    Bertilsson, Sarah
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Glycanmapping of glycoproteins with UPLC-FLR-MALDI/TOF-MS2014Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
  • 126.
    Billinger, Erika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    An investigation of protective formulations containing enzyme inhibitors: Model experiments of trypsin2012Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    This master thesis considers an investigation of protective formulations (ointment, cream) containing enzyme inhibitors. Model experiments have been made on the enzyme trypsin. It is well accepted that feces and urine are an important causing factor for skin irritation (dermatitis) while using diaper. A protective formulation is a physical barrier that separates the harmful substances from the skin. It can also be an active barrier containing active substances, which can be active both towards the skin, and the substances from feces and urine. By preventing contact from these substances the skin will not be harmed, at least for a period of time. A number of different inhibitors were tested towards trypsin and they all showed good inhibition, two of the inhibitors were selected to be immobilized with the help of NHS-­activated Sepharose. Immobilization of these two inhibitors leads to a lesser extent of the risk of developing allergy and also that the possible toxic effect can be minimized. 

  • 127.
    Billinger, Erika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Characterization of conjugated protease inhibitors2020Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The overall theme of this thesis is a step by step approach for the design and characterization of conjugated protease inhibitors. This involves both a new assay method for protease activity and protease inhibition (paper I), a study of the stoichiometry for protease inhibitor interaction (paper II), design of inhibitory peptides (paper IV) and the construction of inhibitor conjugates (paper III & IV).

    (I) A model based primarily on erosion in gelatin for protease activity and inhibition studies was designed. The model was also extended to a separate protective layer covering the layer containing the target substrate. A good correlation between protease concentration and rate of erosion was observed. Similarly, increased concentration of inhibitors gave a systematic decrease in the erosion rate. Kinetic analyses of a two-layer model with substrate in the bottom layer displayed a strict dependence of both inhibitor concentration and thickness of the top “protective” layer.

    (II) The binding stoichiometry between pancreatic proteases and a serine protease inhibitor purified from potato tubers was determined by chromatography-coupled light scattering measurements. This revealed that the inhibitor was able to bind trypsin in a 2:1 complex, whereas the data for a-chymotrypsin clearly showed a limitation to 1:1 complex. The same experiment carried out with elastase and the potato inhibitor gave only weak indications of complex formation under the conditions used.

    (III) A serine protease inhibitor was extracted from potato tubers and conjugated to soluble, prefractionated dextran or inorganic particles. A certain degree of inhibitory activity was retained for both the dextran-conjugated and particle-conjugated inhibitor. The apparent Ki value of the dextran-conjugated inhibitor was found to be in the same range as that for free inhibitor. The dextran conjugate retained a higher activity than the free inhibitor after 1 month of storage at room temperature. Conjugation to oxide particles improved the heat stability of the inhibitor.

    (IV) New synthetic Leupeptin analogues, Ahx-Phe-Leu-Arg-COOH & Ahx-Leu-Leu-Arg-COOH, were synthesized with solid-phase peptide synthesis using Fmoc strategy. These tripeptide inhibitors were tight binding inhibitors to the target enzyme trypsin, similar to the natural occurring leupeptin. The phenylalanine containing synthetic analogue was conjugated to inorganic particles and agarose gel beads. In all cases, the inhibitory activity was well preserved.

    Delarbeid
    1. Kinetic studies of serine protease inhibitors in simple and rapid 'active barrier' model systems: Diffusion through an inhibitor barrier
    Åpne denne publikasjonen i ny fane eller vindu >>Kinetic studies of serine protease inhibitors in simple and rapid 'active barrier' model systems: Diffusion through an inhibitor barrier
    2018 (engelsk)Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 546, s. 43-49Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A model based on gelatin for protease activity studies was designed. The model is also extended to study the efficiency of inhibitors in a separate protective layer covering the layer containing the target substrate. A good correlation between protease concentration and the size of erosion wells formed in a plain gelatin layer was observed. Similarly, increased concentration of inhibitors gave a systematic decrease in well area. Kinetic analyses of the two-layer model in a spectrophotometric plate reader with a fixed concentration of substrate in the bottom layer displayed a strict dependence of both inhibitor concentration and thickness of the top "protective" layer. An apparent, but weaker inhibition effect was also observed without inhibitors due to diffusional and erosion delay of enzyme transport to the substrate-containing layer.

    sted, utgiver, år, opplag, sider
    ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018
    Emneord
    Active barrier, Protease screening, Inhibitor screening, Gelatin model substrate, Protease inhibitors
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-352702 (URN)10.1016/j.ab.2018.01.022 (DOI)000429623500008 ()29408179 (PubMedID)
    Tilgjengelig fra: 2018-06-08 Laget: 2018-06-08 Sist oppdatert: 2019-12-11bibliografisk kontrollert
    2. Light scattering determination of the stoichiometry for protease-potato serine protease inhibitor complexes
    Åpne denne publikasjonen i ny fane eller vindu >>Light scattering determination of the stoichiometry for protease-potato serine protease inhibitor complexes
    2019 (engelsk)Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 582, s. 113357-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The interaction between pancreatic proteases and a serine protease inhibitor purified from potato tubers was investigated by chromatography-coupled light scattering measurements. The molar mass distribution in the chromatogram was compared to theoretical values calculated for the different possible combinations of complexes and free components by three different approaches, namely section analyses of the chromatograms, full mass average determination and mass distribution analysis. This revealed that the inhibitor was able to bind trypsin in a 2:1 complex, whereas the data for chymotrypsin clearly showed a limitation to 1:1 complex regardless of the molar ratio in the injected samples. The same experiment carried out with elastase and the potato inhibitor gave only weak indications of complex formation under the conditions used.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-396981 (URN)10.1016/j.ab.2019.113357 (DOI)
    Tilgjengelig fra: 2019-11-12 Laget: 2019-11-12 Sist oppdatert: 2020-02-17bibliografisk kontrollert
    3. Characterization of Serine Protease Inhibitor from Solanum tuberosum Conjugated to Soluble Dextran and Particle Carriers
    Åpne denne publikasjonen i ny fane eller vindu >>Characterization of Serine Protease Inhibitor from Solanum tuberosum Conjugated to Soluble Dextran and Particle Carriers
    2019 (engelsk)Inngår i: ACS Omega, ISSN 2470-1343, Vol. 4, nr 19, s. 18456-18464Artikkel, forskningsoversikt (Fagfellevurdert) Published
    Abstract [en]

    A serine protease inhibitor was extracted from potato tubers. The inhibitor was conjugated to soluble, prefractionated dextran and titanium dioxide and zinc oxide nanoparticles. Conjugation to dextran was achieved by periodate oxidation of the dextran, followed by Schiff base coupling to inhibitor amino groups, and finally reduction, whereas the conjugation to the oxide particles was carried out by aminosilanization and carbonyldiimidazole activation. The inhibitory effect of the conjugated inhibitor was compared to that of free inhibitor in solution and with gelatin gel as a direct substrate. A certain degree of inhibitory activity was retained for both the dextran-conjugated and particle-conjugated inhibitors. In particular, the apparent Ki value of the dextran-conjugated inhibitor was found to be in the same range as that for free inhibitor. The dextran conjugate retained a higher activity than the free inhibitor after 1 month of storage at room temperature.

    HSV kategori
    Forskningsprogram
    Kemi
    Identifikatorer
    urn:nbn:se:uu:diva-396972 (URN)10.1021/acsomega.9b02815 (DOI)000495089100053 ()31720549 (PubMedID)
    Tilgjengelig fra: 2019-11-12 Laget: 2019-11-12 Sist oppdatert: 2019-12-11bibliografisk kontrollert
    4. Inhibition properties of free and conjugated leupeptin analogues
    Åpne denne publikasjonen i ny fane eller vindu >>Inhibition properties of free and conjugated leupeptin analogues
    (engelsk)Inngår i: Artikkel, forskningsoversikt (Annet vitenskapelig) Submitted
    Abstract [en]

    New synthetic leupeptin analogues Ahx-Phe-Leu-Arg-COOH and Ahx-Leu-Leu-Arg-COOH were prepared by solid-phase peptide synthesis using the Fmoc strategy. The structures were confirmed by mass spectrometry (MS). Determination of the inhibitory properties against trypsin revealed that these tripeptide inhibitors were tight binding inhibitors to their target enzyme, similar to the natural occurring leupeptin and with Ki values generally in the micromolar range. The Ahx-Phe-Leu-Arg-COOH analogue was conjugated to inorganic oxide nanoparticles and agarose gel beads. In all the conjugates, the inhibitory activity was present and in the same range as for the free peptides. 

    Emneord
    Leupeptin analogues, solid-phase peptide synthesis, inorganic carriers, conjugation
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-398908 (URN)
    Tilgjengelig fra: 2019-12-11 Laget: 2019-12-11 Sist oppdatert: 2019-12-11
  • 128.
    Billinger, Erika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Light scattering determination of the stoichiometry for protease-potato serine protease inhibitor complexes2019Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 582, s. 113357-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The interaction between pancreatic proteases and a serine protease inhibitor purified from potato tubers was investigated by chromatography-coupled light scattering measurements. The molar mass distribution in the chromatogram was compared to theoretical values calculated for the different possible combinations of complexes and free components by three different approaches, namely section analyses of the chromatograms, full mass average determination and mass distribution analysis. This revealed that the inhibitor was able to bind trypsin in a 2:1 complex, whereas the data for chymotrypsin clearly showed a limitation to 1:1 complex regardless of the molar ratio in the injected samples. The same experiment carried out with elastase and the potato inhibitor gave only weak indications of complex formation under the conditions used.

  • 129.
    Billinger, Erika
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Johansson, Gunnar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Kinetic studies of serine protease inhibitors in simple and rapid 'active barrier' model systems: Diffusion through an inhibitor barrier2018Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 546, s. 43-49Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A model based on gelatin for protease activity studies was designed. The model is also extended to study the efficiency of inhibitors in a separate protective layer covering the layer containing the target substrate. A good correlation between protease concentration and the size of erosion wells formed in a plain gelatin layer was observed. Similarly, increased concentration of inhibitors gave a systematic decrease in well area. Kinetic analyses of the two-layer model in a spectrophotometric plate reader with a fixed concentration of substrate in the bottom layer displayed a strict dependence of both inhibitor concentration and thickness of the top "protective" layer. An apparent, but weaker inhibition effect was also observed without inhibitors due to diffusional and erosion delay of enzyme transport to the substrate-containing layer.

  • 130.
    Billinger, Erika
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Viljanen, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Lind Bergström, Sara
    Johansson, Gunnar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Inhibition properties of free and conjugated leupeptin analoguesInngår i: Artikkel, forskningsoversikt (Annet vitenskapelig)
    Abstract [en]

    New synthetic leupeptin analogues Ahx-Phe-Leu-Arg-COOH and Ahx-Leu-Leu-Arg-COOH were prepared by solid-phase peptide synthesis using the Fmoc strategy. The structures were confirmed by mass spectrometry (MS). Determination of the inhibitory properties against trypsin revealed that these tripeptide inhibitors were tight binding inhibitors to their target enzyme, similar to the natural occurring leupeptin and with Ki values generally in the micromolar range. The Ahx-Phe-Leu-Arg-COOH analogue was conjugated to inorganic oxide nanoparticles and agarose gel beads. In all the conjugates, the inhibitory activity was present and in the same range as for the free peptides. 

  • 131.
    Billinger, Erika
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Zuo, Shusheng
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Johansson, Gunnar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Characterization of Serine Protease Inhibitor from Solanum tuberosum Conjugated to Soluble Dextran and Particle Carriers2019Inngår i: ACS Omega, ISSN 2470-1343, Vol. 4, nr 19, s. 18456-18464Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    A serine protease inhibitor was extracted from potato tubers. The inhibitor was conjugated to soluble, prefractionated dextran and titanium dioxide and zinc oxide nanoparticles. Conjugation to dextran was achieved by periodate oxidation of the dextran, followed by Schiff base coupling to inhibitor amino groups, and finally reduction, whereas the conjugation to the oxide particles was carried out by aminosilanization and carbonyldiimidazole activation. The inhibitory effect of the conjugated inhibitor was compared to that of free inhibitor in solution and with gelatin gel as a direct substrate. A certain degree of inhibitory activity was retained for both the dextran-conjugated and particle-conjugated inhibitors. In particular, the apparent Ki value of the dextran-conjugated inhibitor was found to be in the same range as that for free inhibitor. The dextran conjugate retained a higher activity than the free inhibitor after 1 month of storage at room temperature.

  • 132.
    Biswas, Srijit
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Watile, Rahul A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Kalek, Marcin
    Himo, Fahmi
    Samec, Joseph S. M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Atom-Efficient Gold(I)-Chloride-Catalyzed Synthesis of alpha-Sulfenylated Carbonyl Compounds from Propargylic Alcohols and Aryl Thiols: Substrate Scope and Experimental and Theoretical Mechanistic Investigation2013Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, nr 52, s. 17939-17950Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gold(I)-chloride-catalyzed synthesis of -sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols showed a wide substrate scope with respect to both propargylic alcohols and aryl thiols. Primary and secondary aromatic propargylic alcohols generated -sulfenylated aldehydes and ketones in 60-97% yield. Secondary aliphatic propargylic alcohols generated -sulfenylated ketones in yields of 47-71%. Different gold sources and ligand effects were studied, and it was shown that gold(I) chloride gave the highest product yields. Experimental and theoretical studies demonstrated that the reaction proceeds in two separate steps. A sulfenylated allylic alcohol, generated by initial regioselective attack of the aryl thiol on the triple bond of the propargylic alcohol, was isolated, evaluated, and found to be an intermediate in the reaction. Deuterium labeling experiments showed that the protons from the propargylic alcohol and aryl thiol were transferred to the 3-position, and that the hydride from the alcohol was transferred to the 2-position of the product. Density functional theory (DFT) calculations showed that the observed regioselectivity of the aryl thiol attack towards the 2-position of propargylic alcohol was determined by a low-energy, five-membered cyclic protodeauration transition state instead of the strained, four-membered cyclic transition state found for attack at the 3-position. Experimental data and DFT calculations supported that the second step of the reaction is initiated by protonation of the double bond of the sulfenylated allylic alcohol with a proton donor coordinated to gold(I) chloride. This in turn allows for a 1,2-hydride shift, generating the final product of the reaction.

  • 133.
    Biswas, Srijit
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Samec, Joseph
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    A Gold(I)-Catalyzed Route to α-Sulfenylated Carbonyl Compounds from Propargylic Alcohols and Aryl Thiols2012Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 48, nr 52, s. 6586-6588Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A one-step atom efficient gold(I)-catalyzed route to α-sulfenylated ketones and aldehydes from propargylic alcohols and aryl thiols is described.

  • 134.
    Biswas, Srijit
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Samec, Joseph
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    The Efficiency of the Metal Catalysts in the Nucleophilic Substitution of Alcohols is Dependent on the Nucleophile and Not on the Electrophile2013Inngår i: Chemistry - An Asian Journal, ISSN 1861-4728, E-ISSN 1861-471X, Vol. 8, nr 5, s. 974-981Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study, we investigate the effect of the electrophiles and the nucleophiles for eight catalysts in the catalytic SN1 type substitution of alcohols with different degree of activation by sulfur-, carbon-, oxygen-, and nitrogen-centered nucleophiles. The catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols and follow the trend of alcohol reactivity. However, when it comes to the nucleophile, the eight catalysts show general and specific variances in the efficiency and selectivity to perform the desired substitution. Interestingly, the selectivity of the alcohols to produce the desired substitution products was found to be independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation. Catalysts based on iron(III), bismuth(III), and gold(III) show higher conversions for S-, C-, and N-centered nucleophiles, and BiIII was the most efficient catalyst in all combinations. Catalysts based on rhenium(I) or rhenium(VII), palladium(II), and lanthanum(III) were the most efficient in performing the nucleophilic substitution on the various alcohols with the O-centered nucleophiles. These catalysts generate the symmetrical ether as a by-product from the reactions of S-, C-, and N-centered nucleophiles as well, resulting in lower chemoselectivity.

  • 135.
    Biswas, Srijit
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Samec, Joseph S. M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Gold-catalyzed route to alpha-sulfenylated carbonyl compounds from propargylic alcohols and thiophenol: Scope, limitations, and mechanism2013Inngår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 245, s. 382-ORGN-Artikkel i tidsskrift (Annet vitenskapelig)
  • 136.
    Biswas, Srijit
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Watile, Rahul A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Samec, Joseph S. M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Tandem Pd/Au-Catalyzed Route to alpha-Sulfenylated Carbonyl Compounds from Terminal Propargylic Alcohols and Thiols2014Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, nr 8, s. 2159-2163Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An efficient and highly atom-economical tandem Pd/Au-catalyzed route to -sulfenylated carbonyl compounds from terminal propargylic alcohols and thiols has been developed. This one-step procedure has a wide substrate scope with respect to substituents at the -position of the alcohol. Both aromatic and aliphatic thiols generated the -sulfenylated carbonyl products in good to excellent yields. A mechanism is proposed in which the reaction proceeds through a Pd-catalyzed regioselective hydrothiolation at the terminal triple bond of the propargyl alcohol followed by an Au-catalyzed 1,2-hydride migration.

  • 137.
    Bivehed, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Strömvall, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bakalkin, Georgy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Andersson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Region-specific bioconversion of dynorphin neuropeptide detected by in situ histochemistry and MALDI imaging mass spectrometry2017Inngår i: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 87, s. 20-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Brain region-specific expression of proteolytic enzymes can control the biological activity of endogenous neuropeptides and has recently been targeted for the development of novel drugs, for neuropathic pain, cancer, and Parkinson's disease. Rapid and sensitive analytical methods to profile modulators of enzymatic activity are important for finding effective inhibitors with high therapeutic value. Combination of in situ enzyme histochemistry with MALDI imaging mass spectrometry allowed developing a highly sensitive method for analysis of brain-area specific neuropeptide conversion of synthetic and endogenous neuropeptides, and for selection of peptidase inhibitors that differentially target conversion enzymes at specific anatomical sites. Conversion and degradation products of Dynorphin B as model neuropeptide and effects of peptidase inhibitors applied to native brain tissue sections were analyzed at different brain locations. Synthetic dynorphin B (2 pmol) was found to be converted to the N-terminal fragments on brain sections whereas fewer C-terminal fragments were detected. N-ethylmaleimide (NEM), a non-selective inhibitor of cysteine peptidases, almost completely blocked the conversion of dynorphin B to dynorphin B(1-6; Leu-Enk-Arg), (1-9), (2-13), and (7-13). Proteinase inhibitor cocktail, and also incubation with acetic acid displayed similar results. Bioconversion of synthetic dynorphin B was region-specific producing dynorphin B(1-7) in the cortex and dynorphin B (2-13) in the striatum. Enzyme inhibitors showed region-and enzyme-specific inhibition of dynorphin bioconversion. Both phosphoramidon (inhibitor of the known dynorphin converting enzyme neprilysin) and opiorphin (inhibitor of neprilysin and aminopeptidase N) blocked cortical bioconversion to dynorphin B(1-7), wheras only opiorphin blocked striatal bioconversion to dynorphin B(2-13). This method may impact the development of novel therapies with aim to strengthen the effects of endogenous neuropeptides under pathological conditions such as chronic pain. Combining histochemistry and MALDI imaging MS is a powerful and sensitive tool for the study of inhibition of enzyme activity directly in native tissue sections. (C) 2016 The Authors. Published by Elsevier Inc.

  • 138.
    Blikstad, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Oxidation of 1,2-Diols Using Alcohol Dehydrogenases: From Kinetic Characterization to Directed Evolution2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The use of enzymes as catalysts for chemical transformations has emerged as a “greener” alternative to traditional organic synthesis. An issue to solve though, is that enzymes are designed by nature to catalyze reactions in a living cell and therefore, in many cases, do not meet the requirements of a suitable biocatalyst. By mimicking Darwinian evolution these problems can be addressed in vitro by different types of directed evolution strategies.

    α-Hydroxy aldehydes and α-hydroxy ketones are important building blocks in the synthesis of natural products, fine chemicals and pharmaceuticals. In this thesis, two alcohol dehydrogenases, FucO and ADH-A, have been studied. Their potentials to serve as useful biocatalysts for the production of these classes of molecules have been investigated, and shown to be good. FucO for its strict regiospecificity towards primary alcohols and that it strongly prefers the S-enantiomer of diol substrates. ADH-A for its regiospecificity towards secondary alcohols, its enantioselectivity and that is has the ability to use a wide variety of bulky substrates. The kinetic mechanisms of these enzymes were investigated using pre-steady state kinetics, product inhibition, kinetic isotope effects and solvent viscosity effects, and in both cases, the rate limiting steps were pin-pointed to conformational changes occurring at the enzyme-nucleotide complex state. These characterizations provide an important foundation for further studies on these two enzymes.  

    FucO is specialized for activity with small aliphatic substrates but is virtually inactive with aryl-substituted compounds. By the use of iterative saturation mutagenesis, FucO was re-engineered and several enzyme variants active with S-3-phenylpropane-1,2-diol and phenylacetaldehyde were obtained. It was shown that these variants capability to act on larger substrates are mainly due to an enlargement of the active site cavity. Furthermore, several amino acids which are important for catalysis and specificity were identified. Phe254 interacts with aryl-substituted substrates through π-π stacking and may be essential for activity with these larger substrates. One mutation caused a loss in the interactions made between the enzyme and the nucleotide and thereby enhanced the turnover number for the preferred substrate

    Delarbeid
    1. Functional characterization of a stereospecific diol dehydrogenase, FucO, from Escherichia coli: substrate specificity, pH dependence, kinetic isotope effects and influence of solvent viscosity
    Åpne denne publikasjonen i ny fane eller vindu >>Functional characterization of a stereospecific diol dehydrogenase, FucO, from Escherichia coli: substrate specificity, pH dependence, kinetic isotope effects and influence of solvent viscosity
    2010 (engelsk)Inngår i: Journal of Molecular Catalysis B: Enzymatic, ISSN 1381-1177, E-ISSN 1873-3158, Vol. 66, nr 1-2, s. 148-155Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    FucO, (S)-1,2-propanediol oxidoreductase, from Escherichia coli is involved in the anaerobic catabolic metabolism of L-fucose and L-rhamnose, catalyzing the interconversion of lactaldehyde to propanediol. The enzyme is specific for the S-enantiomers of the diol and aldehyde suggesting stereospecificity in catalysis. We have studied the enzyme kinetics of FucO with a spectrum of putative alcohol and aldehyde substrates to map the substrate specificity space. Additionally, for a more detailed analysis of the kinetic mechanism, pH dependence of catalysis, stereochemistry in hydride transfer, deuterium kinetic isotope effect of hydride transfer and effect of increasing solvent viscosity were also analyzed. The outcome of this study can be summarized as follows: FucO is highly stereospecific with the highest E-value measured to be 320 for the S-enantiomer of 1,2-propanediol. The enzyme is strictly regiospecific for oxidation of primary alcohols. The enzyme prefers short-chained (2-4 carbons) substrates and does not act on bulkier compounds such as phenyl-substituted alcohols. FucO is an 'A-side' dehydrogenase transferring the pro-R-hydrogen of NADH to the aldehyde substrate. The deuterium KIEs of kcat and kcat/KM were 1.9 and 4.2, respectively, illustrating that hydride transfer is partially rate-limiting but also that other reaction steps contribute to rate limitation of catalysis. Combining the KIE results with the observed effects of increasing medium viscosity proposed a working model for the kinetic mechanism involving slow, rate-limiting, product release and on-pathway conformational changes in the enzyme-nucleotide complexes.

    HSV kategori
    Forskningsprogram
    Biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-123057 (URN)10.1016/j.molcatb.2010.04.010 (DOI)000280928200020 ()
    Tilgjengelig fra: 2010-04-22 Laget: 2010-04-22 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    2. Kinetic characterization of Rhodococcus ruber DSM 44541 alcohol dehydrogenase A
    Åpne denne publikasjonen i ny fane eller vindu >>Kinetic characterization of Rhodococcus ruber DSM 44541 alcohol dehydrogenase A
    2014 (engelsk)Inngår i: Journal of Molecular Catalysis B: Enzymatic, ISSN 1381-1177, E-ISSN 1873-3158, Vol. 99, s. 68-78Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    An increasing interest in biocatalysis and the use of stereoselective alcohol dehydrogenases in synthetic asymmetric catalysis motivates detailed studies of potentially useful enzymes such as alcohol dehydrogenase A (ADH-A) from Rhodococcus ruber. This enzyme is capable of catalyzing enantio-, and regioselective production of phenyl-substituted α-hydroxy ketones (acyloins) which are precursors for the synthesis of a range of biologically active compounds. In this study, we have determined the enzyme activity for a selection of phenyl-substituted vicinal diols and other aryl- or alkyl-substituted alcohols and ketones. In addition, the kinetic mechanism for the oxidation of (R)- and (S)-1-phenylethanol and the reduction of acetophenone has been identified as an Iso Theorell-Chance (hit and run) mechanism with conformational changes of the enzyme-coenzyme binary complexes as rate-determining for the oxidation of (S)-1-phenylethanol and the reduction of acetophenone. The underlying cause of the 270-fold enantiopreference for the (S)-enantiomer of 1-phenylethanol has been attributed to non-productive binding of the R-enantiomer. We have also shown that it is possible to tune the direction of the redox chemistry by adjusting pH with the oxidative reaction being favored at pH values above 7.

    Emneord
    alcohol dehydrogenase, kinetic mechanism, pre-steady state kinetics, product inhibition
    HSV kategori
    Forskningsprogram
    Biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-207474 (URN)10.1016/j.molcatb.2013.10.023 (DOI)000331340500010 ()
    Tilgjengelig fra: 2013-09-15 Laget: 2013-09-15 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    3.
    Posten ble ikke funnet. Det kan skyldes at posten ikke lenger er tilgjengelig eller det er feil id i adressefeltet.
    4. Substrate scope and selectivity in offspring to an enzyme subjected to directed evolution
    Åpne denne publikasjonen i ny fane eller vindu >>Substrate scope and selectivity in offspring to an enzyme subjected to directed evolution
    2014 (engelsk)Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 281, nr 10, s. 2387-2398Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We have analyzed the effects of mutations inserted during directed evolution of a specialized enzyme, Escherichia coli S-1,2-propanediol oxidoreductase (FucO). The kinetic properties of evolved variants have been determined and the observed differences have been rationalized by modeling the tertiary structures of isolated variants and the wild-type enzyme. The native substrate, S-1,2-propanediol, as well as phenylacetaldehyde and 2S-3-phenylpropane-1,2-diol, which are new substrates accepted by isolated variants, were docked into the active sites. The study provides a comprehensive picture of how acquired catalytic properties have arisen via an intermediate generalist enzyme, which had acquired a single mutation (L259V) in the active site. Further mutagenesis of this generalist resulted in a new specialist catalyst. We have also been able to relate the native enzyme activities to the evolved ones and linked the differences to individual amino acid residues important for activity and selectivity. F254 plays a dual role in the enzyme function. First, mutation of F254 into an isoleucine weakens the interactions with the coenzyme thereby increasing its dissociation rate from the active site and resulting in a four-fold increase in turnover number with S-1,2-propanediol. Second, F254 is directly involved in binding of aryl-substituted substrates via π–π interactions. On the other hand, N151 is critical in determining the substrate scope since the side chain amide group stabilizes binding of 1,2-substituted diols and is apparently necessary for enzymatic activity with these substrates. Moreover, the side chain of N151 introduces steric hindrance, which prevents high activity with phenylacetaldehyde. Additionally, the hydroxyl group of T149 is required to maintain the catalytically important hydrogen bonding network.

    HSV kategori
    Forskningsprogram
    Biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-207476 (URN)10.1111/febs.12791 (DOI)000336451900007 ()
    Tilgjengelig fra: 2013-09-15 Laget: 2013-09-15 Sist oppdatert: 2017-12-06bibliografisk kontrollert
  • 139.
    Blikstad, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Dahlström, Kärthe M.
    Åbo Akademi.
    Salminen, Tiina A.
    Åbo Akademi.
    Widersten, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Stereoselective oxidation of aryl-substituted vicinal diols into chiral α-hydroxy aldehydes by re-engineered propanediol oxidoreductase2013Inngår i: ACS Catalysis, ISSN 2155-5435, Vol. 3, nr 12, s. 3016-3025Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    α-Hydroxy aldehydes are chiral building blocks used in synthesis of natural products and synthetic drugs. One route to their production is by regioselective oxidation of vicinal diols and, in this work, we aimed to perform the oxidation of 3-phenyl-1,2-propanediol into the corresponding α‑hydroxy aldehyde applying enzyme catalysis. Propanediol oxidoreductase from E. coli efficiently catalyzes the stereoselective oxidation of S-1,2-propanediol into S-lactaldehyde. The enzyme, however, shows no detectable activity with aryl-substituted or other bulky alcohols. We conducted ISM-driven directed evolution on FucO and were able to isolate several mutants that were active with S-3-phenyl-1,2-propanediol. The most efficient variant displayed a kcat/KM of 40 s-1M-1 and the most enantioselective variant an E-value (S/R) of 80. Furthermore, other isolated variants showed up to 4400-fold increased activity with another bulky substrate, phenylacetaldehyde. The results with engineered propanediol oxidoreductases identified amino acids important for substrate selectivity and asymmetric synthesis of aryl-substituted α-hydroxy aldehydes. In conclusion, our study demonstrates the feasibility of tailoring the catalytic properties of propanediol oxidoreductase for biocatalytic properties.

  • 140.
    Blikstad, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Dahlström, Käthe
    Salminen, Tiina
    Widersten, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Substrate scope and selectivity in offspring to an enzyme subjected to directed evolution2014Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 281, nr 10, s. 2387-2398Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have analyzed the effects of mutations inserted during directed evolution of a specialized enzyme, Escherichia coli S-1,2-propanediol oxidoreductase (FucO). The kinetic properties of evolved variants have been determined and the observed differences have been rationalized by modeling the tertiary structures of isolated variants and the wild-type enzyme. The native substrate, S-1,2-propanediol, as well as phenylacetaldehyde and 2S-3-phenylpropane-1,2-diol, which are new substrates accepted by isolated variants, were docked into the active sites. The study provides a comprehensive picture of how acquired catalytic properties have arisen via an intermediate generalist enzyme, which had acquired a single mutation (L259V) in the active site. Further mutagenesis of this generalist resulted in a new specialist catalyst. We have also been able to relate the native enzyme activities to the evolved ones and linked the differences to individual amino acid residues important for activity and selectivity. F254 plays a dual role in the enzyme function. First, mutation of F254 into an isoleucine weakens the interactions with the coenzyme thereby increasing its dissociation rate from the active site and resulting in a four-fold increase in turnover number with S-1,2-propanediol. Second, F254 is directly involved in binding of aryl-substituted substrates via π–π interactions. On the other hand, N151 is critical in determining the substrate scope since the side chain amide group stabilizes binding of 1,2-substituted diols and is apparently necessary for enzymatic activity with these substrates. Moreover, the side chain of N151 introduces steric hindrance, which prevents high activity with phenylacetaldehyde. Additionally, the hydroxyl group of T149 is required to maintain the catalytically important hydrogen bonding network.

  • 141.
    Blikstad, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Ivarsson, Ylva
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    High-throughput methods for identification of protein-protein interactions involving short linear motifs2015Inngår i: Cell Communication and Signaling, ISSN 1478-811X, E-ISSN 1478-811X, Vol. 13, artikkel-id 38Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Interactions between modular domains and short linear motifs (3-10 amino acids peptide stretches) are crucial for cell signaling. The motifs typically reside in the disordered regions of the proteome and the interactions are often transient, allowing for rapid changes in response to changing stimuli. The properties that make domain-motif interactions suitable for cell signaling also make them difficult to capture experimentally and they are therefore largely underrepresented in the known protein-protein interaction networks. Most of the knowledge on domain-motif interactions is derived from low-throughput studies, although there exist dedicated high-throughput methods for the identification of domain-motif interactions. The methods include arrays of peptides or proteins, display of peptides on phage or yeast, and yeast-two-hybrid experiments. We here provide a survey of scalable methods for domain-motif interaction profiling. These methods have frequently been applied to a limited number of ubiquitous domain families. It is now time to apply them to a broader set of peptide binding proteins, to provide a comprehensive picture of the linear motifs in the human proteome and to link them to their potential binding partners. Despite the plethora of methods, it is still a challenge for most approaches to identify interactions that rely on post-translational modification or context dependent or conditional interactions, suggesting directions for further method development.

  • 142.
    Blom, Elisabeth
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Velikyan, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Hall, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Muhammad, Taj
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Ding, Chenmin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Nair, Manoj
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ga-68-Labeling of RGD peptides and biodistribution2012Inngår i: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, nr 2, s. 165-172Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several peptides comprising Arg-Gly-Asp (RGD) domain and macrocyclic chelator were labeled with Ga-68 for the imaging of angiogenesis. The analogues varied in peptide constitution, linker and chelator type. The labeling efficiency did not vary with the peptide constitution and linker type, but depended on the chelator type. Four of the compounds containing 2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) chelator were labeled at 90 +/- 5 degrees C using conventional or microwave heating reaching 90% of Ga-68 incorporation after 5 and 2 min respectively, when the concentration of the precursor was 2.5 mu M. The compound having 2,2', 2 ''-(1,4,7-triazonane1,4,7-triyl)triacetic acid (NOTA) as the chelator could be labeled at room temperature within 5 min using 2.5 mu M peptide precursor. Two of the compounds contained a poly (ethylene glycol) (PEG) linker to the chelator. The biodistribution of the analogues was studied in male rats.

  • 143.
    Blom, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Purification Processes for Complex Biomacromolecules2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis details various techniques and considerations for the purification of complex biomacromolecules.

     

    Initially an α-mannosidase from babaco fruit was purified using anion exchange-, lectin affinity- and size exclusion chromatography.  The enzyme was approximately 260-280 kDa in size with an apparent an unusual octagonal stoichiometry and displayed properties similar to other known plant α-mannosidases.

     

    Mucins were fractionated by ion exchange and size exclusion chromatography to assess the properties that govern the mucin surface coating interactions in biomaterial research.  Commercially available mucins, of bovine and porcine origin, as wells as crude human mucin were tested. All showed to consist of a population of molecules which differ in size, charge and composition.

     

    The third part of the thesis concerns different aspects of plasmid DNA purification processes.

    A two-step method for analysis of plasmid DNA consisting of size exclusion followed by thiophilic adsorption chromatography was evaluated. It allowed determination of the supercoiled plasmid DNA concentration in all process steps without requirement for extensive sample preparation. This method was shown to be fully comparable in terms of accuracy to capillary gel electrophoresis, considered as the industry standard.

    Purification of plasmid DNA generally involves bacterial cell alkaline lysis, which creates a solution with flocculate material which needs to be removed prior to further processing. The addition of ammonium hydrogen carbonate to the suspension was evaluated to clarify the solution. The released carbon dioxide and ammonium lifts the flocculate to the surface and allows draining of a clear solution. The method is fully scalable, does not affect the plasmid DNA quality and requires no special equipment.

    Thiophilic adsorption chromatography was evaluated for simplification of an existing commercial large scale purification process and was shown to increase both product purity and yields of several tested plasmids. Also, implementation of this step significantly reduced overall production process time.

     

     

     

    Delarbeid
    1. Purification and Characterization of an alpha-Mannosidase from the Tropical Fruit Babaco (Vasconcellea x Heilbornii Cv. Babaco)
    Åpne denne publikasjonen i ny fane eller vindu >>Purification and Characterization of an alpha-Mannosidase from the Tropical Fruit Babaco (Vasconcellea x Heilbornii Cv. Babaco)
    2008 (engelsk)Inngår i: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 56, nr 22, s. 10872-10878Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    An alpha-mannosidase (EC 3.2.1.24) present in the lyophilized latex of babaco (Vasconcellea heilbornii) has been purified to apparent homogeneity by native PAGE. The purification involves a three-step procedure with successive anion exchange with 0 Sepharose HP, lectin affinity chromatography using ConA Sepharose 4B, and gel filtration using Superdex 200 prep grade. The molecular mass was determined to be in the range of 260-280 kDa by Superdex 200 prep grade gel filtration, and isoelectric focusing showed a pI range between 5.85 and 6.55, suggesting different glycosylated isoforms. The optimal temperature for the alpha-mannosidase was determined to lie between 50 and 60 degrees C, and the optimal pH was 4.5 at 50 degrees C. The K-m value for p-nitrophenyl alpha-mannopyranoside (pNPM) was found to be 1.25 mM and the V-max, 2.4 mu kat mg(-1) at 50 degrees C and 1.94 mu kat mg(-1) at 40 degrees C. The pure alpha-mannosidase was specific for mannose and did not display activity for any other tested synthetic substrates.

    Emneord
    alpha-Mannosidase, babaco, latex, purification, characterization, subunit composition
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-107031 (URN)10.1021/jf800857k (DOI)000261056700065 ()
    Tilgjengelig fra: 2009-07-15 Laget: 2009-07-15 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Potential use of mucins as biomaterial coatings. I. Fractionation, characterization, and model adsorption of bovine, porcine, and human mucins
    Åpne denne publikasjonen i ny fane eller vindu >>Potential use of mucins as biomaterial coatings. I. Fractionation, characterization, and model adsorption of bovine, porcine, and human mucins
    2009 (engelsk)Inngår i: Journal of Biomedical Materials Research Part A, ISSN (printed): 1549-3296. (electronic): 1552-4965., Vol. 91A, nr 3, s. 762-772Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Previously, we presented evidence that mucins have potential as   biomaterial coatings. Here, we reveal substantial batch-to-batch   variations for a frequently used commercial bovine salivary mucin   preparation (BSM) and stress the importance of standardizing mucins   intended for comparative purposes. "Mild" fractionation strategies,   aiming at preserving natural mucin functions, were used to prepare two   more defined BSM fractions as well as three mucin fractions from   porcine gastric (PGM) and human salivary (MG1) sources. While the BSM   and PGM were highly purified and mainly adopted random coil   conformations in solution, the MG1 contained mucin-bound components   (1.6 wt% albumin) and appeared compact. Average molar masses and   root-mean-square radii for the predominant BSM, PGM, and MG1 species   spanned 0.8-4.2 MDa and 46-86 nm, respectively. An ellipsometric   evaluation, using hydrophilic and hydrophobic silica, showed the mucin   adsorption to be slow and related to mucin charge, size, conformation,   and compositional complexity. The mass uptakes on hydrophobic silica   averaged 2.6, 2.6, and 5.0 mg/m(2), for BSM, PGM, and MG1,   respectively. Finally, we find that stable mucin coatings can be formed   on polymers of different wettability. The reported mucin preparations   serve as platforms for a series of studies on the biocompatibility of  mucin coatings.

    Emneord
    mucin fractionation, mucin-associated components, size-exclusion chromatograpliy-multiangle light scattering-refractometry (SEC-MALS-RI), biomaterial coating, MUC5B
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-97899 (URN)10.1002/jbm.a.32266 (DOI)000271588800014 ()19051309 (PubMedID)
    Tilgjengelig fra: 2008-11-28 Laget: 2008-11-28 Sist oppdatert: 2012-08-01bibliografisk kontrollert
    3. A chromatographic method for determination of supercoiled plasmid DNA concentration in complex solutions.
    Åpne denne publikasjonen i ny fane eller vindu >>A chromatographic method for determination of supercoiled plasmid DNA concentration in complex solutions.
    2009 (engelsk)Inngår i: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, nr 24, s. 2530-6Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A method for determination of the plasmid DNA concentration with subsequent analysis of the ratio supercoiled to open circular form is presented. The method is suitable for samples from all steps of the manufacturing process, from fermentation to final product. The analysis consists of size exclusion chromatography, followed by analytical thiophilic aromatic chromatography. In the first step, the plasmid DNA concentration is determined by group separation, including removal of RNA and other impurities, within less than 2 min. The limit of detection and quantification was 0.28 and 0.83 microg/ml, respectively. The precision of the method is high, providing a coefficient of variation as low as below 2%. In the second step, the ratio of open circular to supercoiled plasmid DNA is determined following separation of the two plasmid DNA isoforms with a linear salt gradient. The precision of the second step was evaluated using serial injections of aliquots of a sample stock solution. In comparison with the two most commonly used methods, the developed analysis was found to be significantly more accurate than agarose gel electrophoresis and equivalent to capillary gel electrophoresis. The combined methods for quantification and control of homogeneity of plasmid DNA presented here enable reliable and precise analysis at all steps of the manufacturing process.

    Emneord
    Concentration determination, Supercoiled plasmid DNA, Analytical group separation, Thiophilic aromatic chromatography
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot ytbioteknik
    Identifikatorer
    urn:nbn:se:uu:diva-172792 (URN)10.1016/j.jchromb.2009.06.037 (DOI)19616488 (PubMedID)
    Tilgjengelig fra: 2012-04-16 Laget: 2012-04-16 Sist oppdatert: 2017-12-07
    4. Flocculate removal after alkaline lysis in plasmid DNA production.
    Åpne denne publikasjonen i ny fane eller vindu >>Flocculate removal after alkaline lysis in plasmid DNA production.
    2010 (engelsk)Inngår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 29, nr 1, s. 6-10Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Alkaline lysis is the most commonly used method following harvest of bacterial cells for production of plasmid DNA. The method was originally developed for laboratory scale experiments and has shown to be challenging at larger scales. A major problem prior to further downstream processing is the risk of filter clogging without efficient removal of the flocculate that occurs after neutralization. For this purpose we here present a scalable method where the clarification of alkaline lysate is greatly simplified. Through a rapid procedure, involving the addition of ammonium hydrogen carbonate to the neutralized alkaline lysate, the flocculate is lifted to the surface of the solution by the released carbon dioxide and ammonium. After this step a clarified solution can be drained from the bottom of the vessel. The procedure does not impact pH, plasmid DNA concentration or the ratio of open circular to supercoiled plasmid DNA in the solution.

    Emneord
    Alkaline lysis, Plasmid DNA, Flocculate removal
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-172791 (URN)10.1016/j.vaccine.2010.10.021 (DOI)20974301 (PubMedID)
    Tilgjengelig fra: 2012-04-16 Laget: 2012-04-16 Sist oppdatert: 2017-12-07
    5. Scale Up of a Plasmid DNA Purification Process: Use of a Commercial Resin to Produce GMP-Grade pDNA for Clinical Studies
    Åpne denne publikasjonen i ny fane eller vindu >>Scale Up of a Plasmid DNA Purification Process: Use of a Commercial Resin to Produce GMP-Grade pDNA for Clinical Studies
    Vise andre…
    2010 (engelsk)Inngår i: BioProcess International, ISSN 1542-6319, Vol. 8, nr 11, s. 46-54Artikkel i tidsskrift (Fagfellevurdert) Published
    Emneord
    Chromatography, plasmid DNA
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot ytbioteknik
    Identifikatorer
    urn:nbn:se:uu:diva-172889 (URN)
    Tilgjengelig fra: 2012-04-17 Laget: 2012-04-17 Sist oppdatert: 2012-08-01bibliografisk kontrollert
  • 144.
    Blom, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Light-Triggered Conformational Switches for Modulation of Molecular Recognition: Applications for Peptidomimetics and Supramolecular Systems2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The main focus of this thesis is on photochemical modulation of molecular recognition in various host-guest systems. This involves the design, synthesis and integration of light-triggered conformational switches into peptidomimetic guests and molecular tweezer hosts. The impact of the switches on guest and host structures has been assessed by spectroscopic and computational conformational analysis. Effects of photochemical structure modulation on molecular recognition in protein-ligand and supramolecular host-guest systems are discussed.

    Phototriggerable peptidomimetic inhibitors of the enzyme M. tuberculosis ribonucleotide reductase (RNR) were obtained by incorporation of a stilbene based amino acid moiety into oligopeptides between 3-9 residues long (Paper I). Interstrand hydrogen bond probability in the E and Z forms of the peptidomimetics was used as a tool for predicting conformational preferences. Considerable differences in inhibitory potency for the E and Z photoisomers were demonstrated in a binding assay.

    In order to advance the concept of photomodulable inhibitors, synthetic routes towards amino acid derivatives based on the more rigid stiff-stilbene chromophore were developed (Paper II).  The effect of E-Z isomerization on the conformational properties of peptidomimetic inhibitors incorporating the stiff-stilbene chromophore was also assessed computationally (Paper III). It was indicated that inhibitors with the more rigid amino acid derivative should display larger conformational divergence between photoisomers than corresponding stilbene derivatives.

    Bisporphyrin tweezers with enediyne and stiff-stilbene spacers have been synthesized, and the conformational characteristics imposed by the spacers have been studied and compared to a glycoluril linked tweezer. The effects of spacers on tweezer binding of diamine guests and helicity induction by chiral guests have been investigated (Paper IV). Connections between spacer flexibility and host-guest binding strength have been established. The structural properties of the stiff-stilbene spaced tweezer made it particularly susceptible to helicity induction by both monotopic and bitopic chiral guests. Finally, the possibility of photochemical bite-size variation of tweezers with photoswitchable spacers has been assessed. Initial studies have shown that photoisomerization of the tweezers is possible without photochemical decomposition. Conformational analyses indicate that isomerization should impact binding characteristics of the tweezers to a significant extent (Paper V).

    Delarbeid
    1. Phototriggerable peptidomimetics for the inhibition of Mycobacterium turberculosis ribonucleotide reductase by targeting protein-protein binding
    Åpne denne publikasjonen i ny fane eller vindu >>Phototriggerable peptidomimetics for the inhibition of Mycobacterium turberculosis ribonucleotide reductase by targeting protein-protein binding
    Vise andre…
    2015 (engelsk)Inngår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, nr 9, s. 2612-2621Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Incorporation of an artificial amino acid 2 with a stilbene chromophore into peptidomimetics with three to nine amino acids yields phototriggerable candidates for inhibition of the binding between the R1 and R2 subunits of the M. tuberculosis ribonucleotide reductase (RNR). Interstrand hydrogen bond probability was used as a guideline for predicting conformational preferences of the photoisomers. Binding of these inhibitors has been rationalized by docking studies with the R1 unit. Significant differences in binding of the photoisomers were observed. For the shorter peptidomimetics, stronger binding of the Z isomer might indicate hydrophobic interactions between the stilbene chromophore and the binding site.

    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot organisk kemi; Läkemedelskemi
    Identifikatorer
    urn:nbn:se:uu:diva-239491 (URN)10.1039/C4OB01926A (DOI)000350144600018 ()25580895 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council
    Tilgjengelig fra: 2014-12-28 Laget: 2014-12-28 Sist oppdatert: 2018-01-11bibliografisk kontrollert
    2. Synthesis and characterization of photoswitchable stiff-stilbene based amino acid derivatives
    Åpne denne publikasjonen i ny fane eller vindu >>Synthesis and characterization of photoswitchable stiff-stilbene based amino acid derivatives
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Synthetic routes towards the Boc-protected amino acids 1 and 2 incorporating the stiff stilbene chromophore via the corresponding indanone carboxylic acids have been devised. Crucial steps are a reductive McMurry coupling of the indanone carboxylic acids, yielding stiff stilbene dicarboxylic acid esters. Hydrolysis to the monoester and conversion to the azides, followed by a Curtius rearrangement afforded the Boc-protected amino acid ester 1.

    Emneord
    Peptidomimetics
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-267829 (URN)
    Forskningsfinansiär
    Swedish Research Council, 621-2012-3379
    Tilgjengelig fra: 2015-11-27 Laget: 2015-11-27 Sist oppdatert: 2016-01-13
    3. Photoswitchable peptidomimetics with a stiff-stilbene chromophore for inhibition of Mycobacterium tuberculosis RNR
    Åpne denne publikasjonen i ny fane eller vindu >>Photoswitchable peptidomimetics with a stiff-stilbene chromophore for inhibition of Mycobacterium tuberculosis RNR
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Peptidomimetics incorporating two amino acids 1 and 2 with a stiff stilbene chromophore have been screened by a computational study and compared to a previously investigated analog 3 with stilbene chromophore. The effect of E-Z isomerization of the chromophores on the conformational properties of the petidomimetics was assessed via the frequency of hydrogen bonding between the two peptide strands attached to either side of the chromophore. Substantial differences between the three amino acids were thus indicated, in line with the anticipated effect of chromophore rigidity variation.

    Emneord
    Peptidomimetics, conformational analysis
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-267830 (URN)
    Forskningsfinansiär
    Swedish Research Council, 621-2012-3379
    Tilgjengelig fra: 2015-11-27 Laget: 2015-11-27 Sist oppdatert: 2016-01-13
    4. Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis
    Åpne denne publikasjonen i ny fane eller vindu >>Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis
    Vise andre…
    2016 (engelsk)Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 21, nr 1Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar ene-diyne (1), the helical stiff stilbene (2), or the semirigid glycoluril motif fused to  the porphyrins (3) are compared. Binding constants Ka = 10^4 to 10^6 M^-1 reveal subtle  differences between these tweezers, that are discussed in terms of porphyrin dislocation  modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen  guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

    Emneord
    Bisporphyrin tweezers, metalloporphyrins, porphyrinoids, host-guest chemistry, supramolecular chemistry, chirogenesis, chirality transfer, exciton coupled circular dichroism, conformational analysis
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot organisk kemi; Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-267826 (URN)10.3390/molecules21010016 (DOI)000369485600001 ()
    Forskningsfinansiär
    Swedish Research Council, 621-2012-3379Swedish Research Council, 621-2011-4423
    Tilgjengelig fra: 2015-11-27 Laget: 2015-11-27 Sist oppdatert: 2017-12-01bibliografisk kontrollert
    5. Photomodulable bis-porphyrin molecular tweezers as dynamic host systems for diamine guests
    Åpne denne publikasjonen i ny fane eller vindu >>Photomodulable bis-porphyrin molecular tweezers as dynamic host systems for diamine guests
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Bisporphyrin molecular tweezers with an enediyne (1) or a stiff stilbene (2) photoswitchable spacer are proposed as systems for modulation of bitopic binding to diamine guests via E/Z photoisomerization. The photoisomerization has been monitored by UV-Vis and 1H NMR spectroscopy and occurs without side reactions such as Bergman cyclization. Possible applications are rationalized in terms of competitive binding involving monoamine/diamine mixtures, and are supported by conformational analysis of the envisioned host-guest complexes. Binding dynamics for conformationally flexible guests show significantly different performance of aliphatic 1,w-diamine guests with varying N-N distance.

    Emneord
    Bisporphyrin tweezers, supramolecular chemistry, photochemistry
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-267833 (URN)
    Forskningsfinansiär
    Swedish Research Council, 621-2012-3379
    Tilgjengelig fra: 2015-11-27 Laget: 2015-11-27 Sist oppdatert: 2016-01-13
  • 145.
    Blom, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi, Organisk kemi I.
    Photoswitchable peptidomimetics with a stiff-stilbene chromophore for inhibition of Mycobacterium tuberculosis RNRManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Peptidomimetics incorporating two amino acids 1 and 2 with a stiff stilbene chromophore have been screened by a computational study and compared to a previously investigated analog 3 with stilbene chromophore. The effect of E-Z isomerization of the chromophores on the conformational properties of the petidomimetics was assessed via the frequency of hydrogen bonding between the two peptide strands attached to either side of the chromophore. Substantial differences between the three amino acids were thus indicated, in line with the anticipated effect of chromophore rigidity variation.

  • 146.
    Blom, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Synthesis and characterization of photoswitchable stiff-stilbene based amino acid derivativesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Synthetic routes towards the Boc-protected amino acids 1 and 2 incorporating the stiff stilbene chromophore via the corresponding indanone carboxylic acids have been devised. Crucial steps are a reductive McMurry coupling of the indanone carboxylic acids, yielding stiff stilbene dicarboxylic acid esters. Hydrolysis to the monoester and conversion to the azides, followed by a Curtius rearrangement afforded the Boc-protected amino acid ester 1.

  • 147.
    Blom, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Norrehed, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Andersson, Claes-Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Light, Mark E.
    Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, U.K.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis2016Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 21, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar ene-diyne (1), the helical stiff stilbene (2), or the semirigid glycoluril motif fused to  the porphyrins (3) are compared. Binding constants Ka = 10^4 to 10^6 M^-1 reveal subtle  differences between these tweezers, that are discussed in terms of porphyrin dislocation  modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen  guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

  • 148.
    Blom, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Olsson, Sandra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Norrehed, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Andersson, Claes-Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi, Organisk kemi I.
    Photomodulable bis-porphyrin molecular tweezers as dynamic host systems for diamine guestsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Bisporphyrin molecular tweezers with an enediyne (1) or a stiff stilbene (2) photoswitchable spacer are proposed as systems for modulation of bitopic binding to diamine guests via E/Z photoisomerization. The photoisomerization has been monitored by UV-Vis and 1H NMR spectroscopy and occurs without side reactions such as Bergman cyclization. Possible applications are rationalized in terms of competitive binding involving monoamine/diamine mixtures, and are supported by conformational analysis of the envisioned host-guest complexes. Binding dynamics for conformationally flexible guests show significantly different performance of aliphatic 1,w-diamine guests with varying N-N distance.

  • 149.
    Blom, Sofia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Livsmedelsverket.
    Comparison of matrix effects for clean-upmethods for determination of PSP toxins inbivalve mollusks with HILIC UPLC-MS/MS2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 150.
    Blom, Tobias
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Jafri, Hassan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Di Cristo, Valentina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Carva, Karel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Possnert, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Sanyal, Biplab
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi, Organisk kemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Jansson, Ulf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Oorganisk kemi.
    Eriksson, Olle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Leifer, Klaus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Conduction properties of graphene as a function of ion irradiation and acid treatment2011Inngår i: Graphene 2011 - 11th to 14th April 2011. Bilbao, Spain., 2011Konferansepaper (Fagfellevurdert)
1234567 101 - 150 of 1348
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