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  • 1301.
    Yang, Li
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Huang, Xiao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Mamedov, Fikret
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Zhang, Peng
    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, Organisk kemi.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material. Department of Applied Chemistry, Waseda University, Tokyo 169-8555, Japan.
    Conducting redox polymers with non-activated charge transport properties2017Inngår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 19, nr 36, s. 25052-25058Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Non-activated charge transport has been demonstrated in terephthalate-functionalized conducting redox polymers. The transition from a temperature-activated conduction mechanism to a residual scattering mechanism was dependent on the doping level. The latter mechanism is associated with apparent negative activation barriers to charge transport and is generally found in polymer materials with a high degree of order. Crystallographic data, however, suggested a low degree of order in this polymer, indicating the existence of interconnected crystal domains in the predominantly amorphous polymer matrix through which the charge was transported. We have thus shown that the addition of bulky pendant groups to conducting polymers does not prevent efficient charge transport via the residual scattering mechanism with low barriers to charge transport.

  • 1302.
    Yang, Min
    et al.
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden..
    Haase, Claus
    Novo Nordisk AS, Global Res, DK-2880 Bagsvaerd, Denmark..
    Viljanen, Johan V.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Xu, Bingze
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden..
    Ge, Changrong
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden..
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Holmdahl, Rikard
    Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.;Southern Med Univ, Ctr Med Immunopharmacol Res, Guangzhou 510515, Guangdong, Peoples R China..
    Cutting Edge: Processing of Oxidized Peptides in Macrophages Regulates T Cell Activation and Development of Autoimmune Arthritis2017Inngår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 199, nr 12, s. 3937-3942Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    APCs are known to produce NADPH oxidase (NOX) 2-derived reactive oxygen species; however, whether and how NOX2-mediated oxidation affects redox-sensitive immunogenic peptides remains elusive. In this study, we investigated a major immunogenic peptide in glucose-6-phosphate isomerase (G6PI), a potential autoantigen in rheumatoid arthritis, which can form internal disulfide bonds. Ag presentation assays showed that presentation of this G6PI peptide was more efficient in NOX2-deficient (Ncf1(m1J/m1J) mutant) mice, compared with wild-type controls. IFN-gamma-inducible lysosomal thiol reductase (GILT), which facilitates disulfide bond-containing Ag processing, was found to be upregulated in macrophages from Ncf1 mutant mice. Ncf1 mutant mice exhibited more severe G6PI peptide-induced arthritis, which was accompanied by the increased GILT expression in macrophages and enhanced Ag-specific T cell responses. Our results show that NOX2-dependent processing of the redox-sensitive autoantigens by APCs modify T cell activity and development of autoimmune arthritis.

  • 1303.
    Yang, Wenzhi
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Akhtar, Sultan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Leifer, Klaus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Noncovalent Functionalization of Graphene in Suspension2013Inngår i: ISRN Organic Chemistry, ISSN 2090-5149, E-ISSN 2090-5157, nr Article ID 656185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Suspensions of graphene, prepared from graphite foil by sonochemical exfoliation, have been treated with new nonpolar pyrenebutyric amides. The assemblies, in suspension and after deposition on solid supports, were characterized by NMR, absorption, and fluorescence spectroscopy and by transmission electron microscopy, where the well-defined shape and size of an appended [60]fulleropyrrolidine unit facilitates TEM detection of the nonstationary molecules. The accumulated evidence, also including direct comparisons of carbon nanotubes treated with pyrene amides under the same conditions, proves the successful noncovalent functionalization of graphene suspended in non-polar solvent with non-polar pyrene derivatives.

  • 1304. Yaouba, Souaibou
    et al.
    Valkonen, Arto
    Coghi, Paolo
    Gao, Jiaying
    Guantai, Eric M
    Derese, Solomon
    Wong, Vincent K W
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. The Swedish NMR Centre, Gothenburg, Sweden; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden .
    Yenesew, Abiy
    Crystal Structures and Cytotoxicity of ent-Kaurane-Type Diterpenoids from Two Aspilia Species.2018Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, nr 12, artikkel-id 3199Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A phytochemical investigation of the roots of Aspilia pluriseta led to the isolation of ent-kaurane-type diterpenoids and additional phytochemicals (123). The structures of the isolated compounds were elucidated based on Nuclear Magnetic Resonance (NMR) spectroscopic and mass spectrometric analyses. The absolute configurations of seven of the ent-kaurane-type diterpenoids (36, 6b, 7 and 8) were determined by single crystal X-ray diffraction studies. Eleven of the compounds were also isolated from the roots and the aerial parts of Aspilia mossambicensis. The literature NMR assignments for compounds 1 and 5 were revised. In a cytotoxicity assay, 12α-methoxy-ent-kaur-9(11),16-dien-19-oic acid (1) (IC50 = 27.3 ± 1.9 µM) and 9β-hydroxy-15α-angeloyloxy-ent-kaur-16-en-19-oic acid (3) (IC50 = 24.7 ± 2.8 µM) were the most cytotoxic against the hepatocellular carcinoma (Hep-G2) cell line, while 15α-angeloyloxy-16β,17-epoxy-ent-kauran-19-oic acid (5) (IC50 = 30.7 ± 1.7 µM) was the most cytotoxic against adenocarcinomic human alveolar basal epithelial (A549) cells.

  • 1305.
    Ye, Sofie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Rhodium-Catalyzed Hydroarylation of Fullerene C60 with Boronic Acids2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 1306. Ye, Weihua
    et al.
    Lind, Jesper
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Maler, Lena
    Characterization of the Morphology of Fast-Tumbling Bicelles with Varying Composition2014Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 30, nr 19, s. 5488-5496Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Small, fast-tumbling bicelles are frequently used in solution NMR studies of protein lipid interactions. For this purpose it is critical to have information about the organization of the lipids within the bicelle structure. We have studied the morphology of small, fast-tumbling bicelles containing DMPC and DHPC as a function of temperature, lipid concentration, and the relative ratio (q value) of lipid (DMPC) to detergent (DHPC) amounts. Dynamic light scattering and cryo-transmission electron microscopy techniques were used to measure the size of the bicelles and to monitor the shape and dispersity of the particles in the samples. The stability and size of DMPC-containing bicelle mixtures were found to be highly dependent on temperature and the total lipid concentration for mixtures with q = 1 and q = 1.5. Stable DMPC/DHPC bicelles are only formed at low q values (0.5). Bicelle mixtures with q > 0.5 appear to be multidisperse containing more than one component, one with r(H) around 2.5 nm and one with r(H) of 6-8 nm. This is interpreted as a coexistence of small (possibly mixed micelles) bicelles and much larger bicelles. Incubating the sample at 37 degrees C increases the phase separation. Moreover, low total amphiphile concentrations and low q values lead to the formation of a temperature-independent morphology, interpreted as the formation of small particles in which the DHPC and DMPC are more mixed. On the basis of these results, we propose the existence of a critical bicelle concentration, a parameter that determines the existence of bilayered bicelles, which varies with q value. This polymorphism was not observed at any concentrations for q = 0.5 bicelles, for which a small but detectable temperature dependence was observed at high concentrations. The results demonstrate that q = 0.5 mixtures predominantly form "classical" bicelles, but that caution is needed when using fast-tumbling mixtures with q values higher than 0.5.

  • 1307.
    Yngve, U
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Hedberg, E
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Synthesis of N-succinimidyl-4-76Br-bromobenzoate and its use in conjugation to proteins and 5´modified oligonucleotides1997Inngår i: Journal of Labelled Compounds and Radiopharmaceuticals, ISSN 0362-4803, Vol. 40, s. 120-121Artikkel i tidsskrift (Fagfellevurdert)
  • 1308.
    Yngve, Ulrika
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Khan, Tanweera Shaheena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Bergström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Långstrom, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Labelling of octreotide using Br-76-prosthetic groups2001Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 44, nr 8, s. 561-573Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A method for labelling the octapeptide octreotide (D-Phe-Cys-Phe-D-TrpLys-Thr-Cys-Thr(ol)) with the positron emitting Br-76 (T-1/2 = 16 h) is presented. epsilon -Boc-protected octreotide was conjugated to N-succinimidyl 4-[Br-76]bromobenzoate 1 and N-succinimidyl 5-[Br-76]bromo-3-pyridinecarboxylate 3 using microwave heating. The conjugates 4 and 5 were isolated in 50-55% radiochemical yield after the removal of the protecting Boc-group. Compound 3 was synthesised from the corresponding trimethylstannyl-precursor in 25% radiochemical yield. The synthesis of methyl-4-[Br-76] bromobenzimidate 8 in 40% radiochemical yield from the precursor methyl -4-trimethylstannylbenzimidate is also described. Experiments were performed to react 8 with Boc-octreotide but no product was obtained. The binding-properties of Br-76-conjugates 4 and 5 to meningiomas were investigated using frozen section autoradiography. Compound 5 showed better binding properties than 4.

  • 1309. Yotapan, Nattawut
    et al.
    Paptchikhine, Alexander
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Bera, Milan
    Avula, Satya Kumar
    Vilaivan, Tirayut
    Andersson, Pher G.
    Simple Proline-Derived Phosphine-Thiazole Iridium Complexes for Asymmetric Hydrogenation of Trisubstituted Olefins2013Inngår i: Asian Journal of Organic Chemistry, ISSN 2193-5807, Vol. 2, nr 8, s. 674-680Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Proline-based phosphine-thiazole/imidazole ligands have been synthesized and successfully applied in the homogeneous, iridium-catalyzed, asymmetric hydrogenation of trisubstituted functionalized and unfunctionalized olefins. Five different sets of ligands were prepared then evaluated for their catalytic activity and enantioselectivity in asymmetric hydrogenation.

  • 1310. Young, Gavin
    et al.
    Hundt, Nikolas
    Cole, Daniel
    Fineberg, Adam
    Andrecka, Joanna
    Tyler, Andrew
    Olerinyova, Anna
    Ansari, Ayla
    Marklund, Erik G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Collier, Miranda P.
    Chandler, Shane A.
    Tkachenko, Olga
    Allen, Joel
    Crispin, Max
    Billington, Neil
    Takagi, Yasuharu
    Sellers, James R.
    Eichmann, Cédric
    Selenko, Philipp
    Frey, Lukas
    Riek, Roland
    Galpin, Martin R.
    Struwe, Weston B.
    Benesch, Justin L. P.
    Kukura, Philipp
    Quantitative mass imaging of single biological macromolecules2018Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 360, nr 6387, s. 423-427Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Careful measurements of light scattering can provide information on individual macromolecules and complexes. Young et al. used a light-scattering approach for accurate mass determination of proteins as small as 20 kDa (see the Perspective by Lee and Klenerman). Movies of protein complex association and dissociation were analyzed to extract biophysical parameters from single molecules and assemblies without labeling. Using this approach, the authors determined in vitro kinetics of fibril and aggregate growth and association constants for a complex protein-glycoprotein assembly.Science, this issue p. 423; see also p. 378The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.

  • 1311.
    Yu, Hans
    et al.
    Univ Bodenkultur Wien, Interuniv Dept Agrobiotechnol IFA Tulln, Inst Biotechnol Anim Prod, Tulln, Austria.;Univ Vet Med Vienna, Dept Biomed Sci, Inst Anim Breeding & Genet, Vienna, Austria..
    Reiser, Judith
    Ludwig Maximilians Univ Munchen, Inst Mol Anim Breeding & Biotechnol, Munich, Germany..
    Besenfelder, Urban
    Univ Bodenkultur Wien, Interuniv Dept Agrobiotechnol IFA Tulln, Inst Biotechnol Anim Prod, Tulln, Austria.;Univ Vet Med Vienna, Reprod Ctr Wieselburg, Vienna, Austria..
    Razzazi-Fazeli, Ebrahim
    Univ Vet Med Vienna, VetCore Facil Res, Vienna, Austria..
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Brem, Gottfried
    Univ Bodenkultur Wien, Interuniv Dept Agrobiotechnol IFA Tulln, Inst Biotechnol Anim Prod, Tulln, Austria.;Univ Vet Med Vienna, Dept Biomed Sci, Inst Anim Breeding & Genet, Vienna, Austria..
    Artemenko, Konstantin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mayrhofer, Corina
    Univ Bodenkultur Wien, Interuniv Dept Agrobiotechnol IFA Tulln, Inst Biotechnol Anim Prod, Tulln, Austria.;Univ Vet Med Vienna, Dept Biomed Sci, Inst Anim Breeding & Genet, Vienna, Austria..
    Exploring the oviductal fluid proteome by a lectin-based affinity approach2016Inngår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 16, nr 23, s. 2962-2966Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The analysis of glycoproteins in body fluids represents a central task in the study of vital processes. Herein, we assessed the combined use of Concanavalin A and Wheat Germ Agglutinin as ligands to fractionate and enrich glycoproteins from oviductal fluid (OF), which is a source of molecules involved in fertilization. First, the selectivity was corroborated by a gel-based approach using glycoprotein staining and enzymatic deglycosylation. Nanoliquid chromatography-tandem mass spectrometry (nLC-ESI-MS/MS) further allowed the reliable identification of 134 nonbound as well as 130 lectin-bound OF proteins. Enrichment analysis revealed that 77% of the annotated proteins in the lectin-bound fraction were known glycoproteins (p-value [FDR] = 1.45E-31). The low variance of the number of peptide spectrum matches for each protein within replicates indicated a consistent reproducibility of the whole workflow (median CV 17.3% for technical replicates and 20.7% for biological replicates). Taken together, this study highlights the applicability of a lectin-based workflow for the comprehensive analysis of OF proteins and gives for the first time an insight into the broad glycoprotein content of OF.

  • 1312.
    Zanni, Giulia
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Brain Repair & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Michno, Wojciech
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Di Martino, Elena
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Tjärnlund-Wolf, Anna
    Univ Gothenburg, Sahlgrenska Acad, Ctr Brain Repair & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mason, Charlotte Elizabeth
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Hellspong, Gustaf
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Blomgren, Klas
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pediat Oncol, Stockholm, Sweden..
    Hanrieder, Jorg
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;Chalmers, Dept Chem & Chem Engn, Gothenburg, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, London WC1E 6BT, England..
    Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 40726Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry-(ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

  • 1313.
    Zayny, Ahmad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Almokhtar, Mokhtar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Wikvall, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Ubhayasekera, Kumari
    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.
    Kibar, Pinar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Norlin, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Effects of glucocorticoids on vitamin D3-metabolizing 24-hydroxylase (CYP24A1) in Saos-2 cells and primary human osteoblasts2019Inngår i: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 496, artikkel-id 110525Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vitamin D is essential for bone function and deficiency in active vitamin D hormone can lead to bone disorders. Long-term treatment with glucocorticoids results in osteoporosis and increased risk of fractures. Much remains unclear regarding the effects of these compounds in bone cells. In the current study, human osteosarcoma Saos-2 cells and primary human osteoblasts were found to express mRNA for the vitamin D receptor as well as activating and deactivating enzymes in vitamin D-3 metabolism. These bone cells exhibited CYP24A1-mediated 24-hydroxylation which is essential for deactivation of the active vitamin form. However, bioactivating vitamin D-3 hydroxylase activities could not be detected in either of these cells. Several glucocorticoids, including prednisolone, down regulated CYP24A1 mRNA and CYP24A1-mediated 24-hydroxylase activity in both Saos-2 and primary human osteoblasts. Also, prednisolone significantly suppressed a human CYP24A1 promoter-luciferase reporter gene in Saos-2 cells co-transfected with the glucocorticoid receptor. Thus, the results of the present study show suppression by glucocorticoids on CYP24A1 mRNA, CYP24A1-mediated metabolism and CYP24A1 promoter activity in human osteoblast-like cells. As part of this study we examined if glucocorticoids are formed locally in Saos-2 cells. The experiments indicate formation of 11-deoxycortisol, a steroid with glucocorticoid activity, which can bind the glucocorticoid receptor. Our data showing suppression by glucocorticoids on CYP24A1 expression in human osteoblasts suggest a previously unknown mechanism for effects of glucocorticoids in human bone, where these compounds may interfere with regulation of active vitamin D levels.

  • 1314.
    Zayny, Ahmad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Almokhtar, Mokhtar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Wikvall, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ubhayasekera, S. J. Kumari A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergqvist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Norlin, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Effects of glucocorticoids on vitamin D3 24-hydroxylase (CYP24A1) in Saos-2 cells and primary human osteoblastsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Vitamin D is essential for bone function and deficiency in active vitamin D hormone can lead to rickets, osteomalacia or osteoporosis. Long-term treatment with glucocorticoids is known to result in osteoporosis and a substantially increased risk of fractures. Although the actions of vitamin D and glucocorticoids play important roles for bone function and in the development of osteoporosis, much remains unclear regarding the effects of these compounds in cells of the bone. In the current study, the human osteosarcoma Saos-2 cell line and primary human osteoblast-like cells were found to express mRNA for the vitamin D receptor as well as both activating and deactivating enzymes in vitamin D3 metabolism. These bone cells exhibited the CYP24A1-mediated 24-hydroxylation, involved in deactivation of the active vitamin D3 form. However, bioactivating vitamin D3 hydroxylase activities could not be detected in either of these cells. Several commonly used therapeutic glucocorticoids, including prednisolone, down regulated mRNA expression for the CYP24A1 gene as well as the CYP24A1-mediated 24-hydroxylase activity in both Saos-2 and primary human osteoblast-like cells. Prednisolone had the strongest suppressive effect on CYP24A1 expression. Results from experiments with a human CYP24A1 promoter-luciferase reporter gene in Saos-2 cells, co-transfected with the glucocorticoid receptor, showed that treatment with prednisolone significantly suppresses the CYP24A1 promoter activity. Thus, the results of the present study showed suppression by glucocorticoids on expression of CYP24A1 mRNA, CYP24A1-mediated metabolism and CYP24A1 promoter activity in human osteoblast-like cells. As part of the present investigation we examined if glucocorticoids are formed locally in Saos-2 cells. The experiments indicate formation of 11-deoxycortisol, a steroid that has glucocorticoid activity and is able to bind to the glucocorticoid receptor.

    Our data showing suppression by glucocorticoids on CYP24A1 expression in human osteoblast-like cells suggest a previously unknown mechanism for effects of glucocorticoids in human bone, where these compounds may act by increasing the normal levels of active vitamin D.

  • 1315.
    Zeleskov, Dianna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    The hunt after a monooxygenase for styrene epoxidation: Extending an artificial synthetic pathway in E. coli2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 1316.
    Zhan, Shaoqi
    et al.
    KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Martensson, Daniel
    KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Purg, Miha
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Kamerlin, Shina C. Lynn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Ahlquist, Marten S. G.
    KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Capturing the Role of Explicit Solvent in the Dimerization of Ru-V(bda) Water Oxidation Catalysts2017Inngår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 56, nr 24, s. 6962-6965Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A ground-breaking empirical valence bond study for a soluble transition-metal complex is presented. The full reaction of catalyst monomers approaching and reacting in the Ru-V oxidation state were studied. Analysis of the solvation shell in the reactant and along the reaction coordinate revealed that the oxo itself is hydrophobic, which adds a significant driving force to form the dimer. The effect of the solvent on the reaction between the prereactive dimer and the product was small. The solvent seems to lower the barrier for the isoquinoline (isoq) complex while it is increased for pyridines. By comparing the reaction in the gas phase and solution, the proposed p-stacking interaction of the isoq ligands is found to be entirely driven by the water medium.

  • 1317.
    Zhang, Jian
    et al.
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Poongavanam, Vasanthanathan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark..
    Kang, Dongwei
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Bertagnin, Chiara
    Univ Padua, Dept Mol Med, Via Gabelli 63, I-35121 Padua, Italy..
    Lu, Huamei
    Shandong Acad Agr Sci, Inst Poultry Sci, 1 Jiaoxiao Rd, Jinan 250023, Shandong, Peoples R China..
    Kong, Xiujie
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Ju, Han
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Lu, Xueyi
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Gao, Ping
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Tian, Ye
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Jia, Haiyong
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Desta, Samuel
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Ding, Xiao
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Sun, Lin
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Fang, Zengjun
    Shandong Univ, Hosp 2, 247 Beiyuan Ave, Jinan 250033, Shandong, Peoples R China..
    Huang, Boshi
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Liang, Xuewu
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Jia, Ruifang
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Ma, Xiuli
    Shandong Acad Agr Sci, Inst Poultry Sci, 1 Jiaoxiao Rd, Jinan 250023, Shandong, Peoples R China..
    Xu, Wenfang
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Murugan, Natarajan Arul
    KTH Royal Inst Technol, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden..
    Loregian, Arianna
    Univ Padua, Dept Mol Med, Via Gabelli 63, I-35121 Padua, Italy..
    Huang, Bing
    Shandong Acad Agr Sci, Inst Poultry Sci, 1 Jiaoxiao Rd, Jinan 250023, Shandong, Peoples R China..
    Zhan, Peng
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Liu, Xinyong
    Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China..
    Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of Group-1 and-2 Influenza A Neuraminidases, Including a Drug-Resistant Variant2018Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, nr 14, s. 6379-6397Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    On the basis of our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Among the synthesized compounds, 15b and 15c were exceptionally active against both group-1 and -2 NAs. Especially for 09N1, N2, N6, and N9 subtypes, they showed 6.80-12.47 and 1.20-3.94 times greater activity than oseltamivir carboxylate (OSC). They also showed greater inhibitory activity than OSC toward H274Y and E119V variant. In cellular assays, they exhibited greater potency than OSC toward H5N1, H5N2, H5N6, and H5N8 viruses. 15b demonstrated high metabolic stability, low cytotoxicity in vitro, and low acute toxicity in mice. Computational modeling and molecular dynamics studies provided insights into the role of R group of 15b in improving potency toward group-1 and -2 NAs. We believe the successful exploitation of the 150-cavity of NAs represents an important breakthrough in the development of more potent anti-influenza agents.

  • 1318.
    Zhang, Jinbao
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Ellis, Hanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Yang, Lei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Johansson, Erik M. J.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Boschloo, Gerrit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Vlachopoulos, Nick
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Hagfeldt, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    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.
    Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Analysis of Poly(3,4-ethylenedioxythiophene) in Solid-State Dye-Sensitized Solar Cells: Comparison of In Situ Photoelectrochemical Polymerization in Aqueous Micellar and Organic Media2015Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, nr 7, s. 3942-3948Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Solid-state dye-sensitized solar cells (sDSCs) are devoid of such issues as electrolyte evaporation or leakage and electrode corrosion, which are typical for traditional liquid electrolyte-based DSCs. Poly(3,4-ethylenedioxythiophene) (PEDOT) is one of the most popular and efficient p-type conducting polymers that are used in sDSCs as a solid-state hole-transporting material. The most convenient way to deposit this insoluble polymer into the dye-sensitized mesoporous working electrode is in situ photoelectrochemical polymerization. Apparently, the structure and the physicochemical properties of the generated conducting polymer, which determine the photovoltaic performance of the corresponding solar cell, can be significantly affected by the preparation conditions. Therefore, a simple and fast analytical method that can reveal information on polymer chain length, possible chemical modifications, and impurities is strongly required for the rapid development of efficient solar energy-converting devices. In this contribution, we applied matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) for the analysis of PEDOT directly on sDSCs. It was found that the PEDOT generated in aqueous micellar medium possesses relatively shorter polymeric chains than the PEDOT deposited from an organic medium. Furthermore, the micellar electrolyte promotes a transformation of one of the thiophene terminal units to thiophenone. The introduction of a carbonyl group into the PEDOT molecule impedes the growth of the polymer chain and reduces the conductivity of the final polymer film. Both the simplicity of sample preparation (only application of the organic matrix onto the solar cell is needed) and the rapidity of analysis hold the promise of making MALDI MS an essential tool for the physicochemical characterization of conducting polymer-based sDSCs.

  • 1319.
    Zhang, Wei
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Dourado, Daniel F. A. R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Fernandes, Pedro
    Universidade do Porto Rua do Campo Alegre.
    Ramos, Maria
    Universidade do Porto Rua do Campo Alegre.
    Mannervik, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Multidimensional epistasis and fitness landscapes in enzyme evolution2012Inngår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 445, s. 39-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The conventional analysis of enzyme evolution is to regard one single salient feature as a measure of fitness, expressed in a milieu exposing the possible selective advantage at a given time and location. Given that a single protein may serve more than one function, fitness should be assessed in several dimensions. In the present study we have explored individual mutational steps leading to a triple-point-mutated human GST (glutathione transferase) A2-2 displaying enhanced activity with azathioprine. A total of eight alternative substrates were used to monitor the diverse evolutionary trajectories. The epistatic effects of the imitations on catalytic activity were variable in sign and magnitude and depended on the substrate used, showing that epistasis is a multidimensional quality. Evidently, the multidimensional fitness landscape can lead to alternative trajectories resulting in enzymes optimized for features other than the selectable markers relevant at the origin of the evolutionary process. In this manner the evolutionary response is robust and can adapt to changing environmental conditions.

  • 1320.
    Zhang, Wei
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Dourado, Daniel F. A. R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Mannervik, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Evolution of the active site of human glutathione transferase A2-2 for enhanced activity with dietary isothiocyanates2015Inngår i: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1850, nr 4, s. 742-749Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Organic isothiocyanates (ITCs) are produced by plants, in which they are released from glucosinolates by myrosinase. ITCs are generally toxic and serve as a chemical defense against herbivorous insects and against infections by microorganisms. In mammalian tissues subtoxic concentrations of ITCs can provide protective effects against cancer and other diseases partially by induction of glutathione transferases (GSTs) and other detoxication enzymes. Thus, human consumption of edible plants rich in ITCs is presumed to provide health benefits. ITCs react with intracellular glutathione to form dithiocarbamates, catalyzed by GSTs. Formation of glutathione conjugates is central to the biotransformation of ITCs and leads to a route for their excretion. Clearly, the emergence of ITC conjugating activity in GSTs is essential from the biological and evolutionary perspective. Methods: In the present investigation an active-site-focused mutant library of GST A2-2 has been screened for enzyme variants with enhanced ITC activity. Results: Significantly superior activities were found in 34 of the approximately 2000 mutants analyzed, and the majority of the superior GSTs featured His and Gly residues in one of the three active-site positions subjected to mutagenesis. Conclusions: We explored the propensity of GSTs to obtain altered substrate selectivity and moreover, identified a specific pattern of mutagenesis in GST for enhanced PEITC detoxification, which may play an important role in the evolution of adaptive responses in organisms subjected to ITCs. General significance: The facile acquisition of enhanced ITC activity demonstrates that this important detoxication function can be promoted by numerous evolutionary trajectories in sequence space. (C) 2014 Elsevier B.V. All rights reserved.

  • 1321.
    Zhang, Wei
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi, Biokemi.
    Mannervik, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    An improved dual-tube megaprimer approach for multi-site saturation mutagenesis2013Inngår i: World Journal of Microbiology & Biotechnology, ISSN 0959-3993, E-ISSN 1573-0972, Vol. 29, nr 4, s. 667-672Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Saturation mutagenesis is a powerful tool in protein engineering. Even though QuikChange site-directed mutagenesis method is dominantly used in laboratories, it could not be successfully applied to the generation of a focused mutant library of human glutathione transferase A2-2. In the present study, we further developed an improved versatile dual-tube approach of randomizing difficult-to-amplify targets, exhibiting significant improvement towards equal distribution of nucleotides at randomized sites compared to other published methods.

  • 1322.
    Zhang, Xinchen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Interaction of PEG-ylated Lipid Nanoparticles with Silica Substrates2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    In this project, the interaction between polyethylene glycol modified (PEG-ylated) lipid nanoparticles and silica substrates was studied to find out how this interaction was affected by bulk concentration, temperature and the composition of particles. One kind of lipodisk and four kinds of PEG-ylated liposome were prepared from lipid films and characterized by quartz crystal microbalance with dissipation monitoring (QCM-D) instrument mounted with silica sensor. The detailed information of particle-silica interaction could be obtained from the raw data, frequency and dissipation values, and the adsorbed mass surface density calculated from the raw data. Lipodisks could be immobilized on the silica surface. Whether they would be rinsed away by PBS buffer was influenced by both the bulk concentration and temperature. The way of their binding could change and the changing process was affected by temperature. PEG-ylated liposomes could also be immobilized on the silica surface, and they could break and spread to form supported lipid bilayer in certain conditions, for example, the changing of temperature or the using of certain lipids. Supported lipid bilayers were created with high reproducibility in this project, which could be very useful to the future study of transmembrane proteins functions and lipodisk properties.

  • 1323.
    Zhang, Yuan
    et al.
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Wang, Dan
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China;Binzhou Med Univ, Affiliated Hosp, Dept Radiol, 661 Second Huanghe Rd, Binzhou 256603, Shandong, Peoples R China.
    Li, Min
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Wei, Xiaodan
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Liu, Shuang
    Binzhou Med Univ, Coll Enol, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Zhao, Miaoqing
    Shandong Univ, Prov Hosp, Dept Pathol, 324 Jingwu Weiqi Rd, Jinan 250021, Shandong, Peoples R China.
    Liu, Chu
    Yantai Yuhuangding Hosp, Dept Urol, 20 Yuhuangding East Rd, Yantai 264000, Shandong, Peoples R China.
    Wang, Xizhen
    Weifang Med Univ, Affiliated Hosp, Imaging Ctr, 465 Yuhe Rd, Weifang 256603, Shandong, Peoples R China.
    Jiang, Xingyue
    Binzhou Med Univ, Affiliated Hosp, Dept Radiol, 661 Second Huanghe Rd, Binzhou 256603, Shandong, Peoples R China.
    Li, Xuri
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Zhang, Shuping
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Bergquist, Jonas
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Wang, Bin
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Yang, Chunhua
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Mi, Jia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Tian, Geng
    Binzhou Med Univ, Med & Pharm Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Quantitative Proteomics of TRAMP Mice Combined with Bioinformatics Analysis Reveals That PDGF-B Regulatory Network Plays a Key Role in Prostate Cancer Progression2018Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 17, nr 7, s. 2401-2411Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice is a widely used transgenic animal model of prostate cancer (PCa). We performed a label-free quantitative proteomics analysis combined with a bioinformatics analysis on the entire prostate protein extraction from TRAMP mice and compared it with WT littermates. From 2379 total identified proteins, we presented a modest mice prostate reference proteome containing 919 proteins. 61 proteins presented a significant expression difference between two groups. The integrative bioinformatics analysis predicted the overexpression of platelet-derived growth factor B (PDGF-B) in tumor tissues and supports the hypothesis of the PDGF-B signaling network as a key upstream regulator in PCa progression. Furthermore, we demonstrated that Crenolanib, a novel PDGF receptor inhibitor, inhibited PCa cell proliferation in a dose-dependent manner. Finally, we revealed the importance of PDGF-B regulatory network in PCa progression, which will assist us in understanding the role and mechanisms of PDGF-B in promoting cancer growth and provide valuable knowledge for future research on anti-PDGF therapy.

  • 1324.
    Zhao, Hongxing
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Chen, Maoshan
    Monash Univ, Cent Clin Sch, Australian Ctr Blood Dis, Clayton, Vic, Australia.
    Valdes, Alberto
    Univ Alcala De Henares, Dept Analyt Chem Phys Chem & Chem Engn, Madrid, Spain.
    Lind, Sara
    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, Medicinsk genetik och genomik.
    Transcriptomic and proteomic analyses reveal new insights into the regulation of immune pathways during adenovirus type 2 infection2019Inngår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 19, artikkel-id 15Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Human adenovirus (Ad) infection leads to the changes of host cell gene expression and biosynthetic processes. Transcriptomics in adenovirus type 2 (Ad2)-infected lung fibroblasts (IMR-90) cells has previously been studied using RNA sequencing. However, this study included only two time points (12 and 24 hpi) using constrained 76bp long sequencing reads. Therefore, a more detailed study of transcription at different phases of infection using an up-graded sequencing technique is recalled. Furthermore, the correlation between transcription and protein expression needs to be addressed.

    Results: In total, 3556 unique cellular genes were identified as differentially expressed at the transcriptional level with more than 2-fold changes in Ad2-infected cells as compared to non-infected cells by using paired-end sequencing. Based on the kinetics of the gene expression changes at different times after infection, these RNAs fell into 20 clusters. Among them, cellular genes involved in immune response were highly up-regulated in the early phase before becoming down-regulated in the late phase. Comparison of differentially expressed genes at transcriptional and posttranscriptional levels revealed low correlation. Particularly genes involved in cellular immune pathways showed a negative correlation. Here, we highlight the genes which expose inconsistent expression profiles with an emphasis on key factors in cellular immune pathways including NFB, JAK/STAT, caspases and MAVS. Different from their transcriptional profiles with up- and down-regulation in the early and late phase, respectively, these proteins were up-regulated in the early phase and were sustained in the late phase. A surprising finding was that the target genes of the sustained activators failed to show response.

    Conclusion: There were features common to genes which play important roles in cellular immune pathways. Their expression was stimulated at both RNA and protein levels during the early phase. In the late phase however, their transcription was suppressed while protein levels remained stable. These results indicate that Ad2 and the host cell use different strategies to regulate cellular immune pathways. A control mechanism at the post-translational level must thus exist which is under the control of Ad2.

  • 1325.
    Zhao, Hongxing
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Chen, Moashan
    Bergström Lind, Sara
    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, Medicinsk genetik och genomik.
    Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection2016Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 492, s. 242-250Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The deregulation of cellular long non-coding RNA (lncRNA) expression during a human adenovirus infection was studied by deep sequencing. Expression of lncRNAs increased substantially following the progression of the infection. Among 645 significantly expressed lncRNAs, the expression of 398 was changed more than 2-fold. More than 80% of them were up-regulated and 80% of them were detected during the late phase. Eased on the genomic locations of the deregulated lncRNAs in relation to known mRNAs and miRNAs, they were predicted to be involved in growth, structure, apoptosis and wound healing in the early phase, cell proliferation in the intermediate phase and protein synthesis, modification and transport in the late phase. The most significant functions of cellular RNA-binding proteins, previously shown to interact with the deregulated lncRNAs identified here, are involved in RNA splicing, nuclear export and translation events. We hypothesize that adenoviruses exploit the lncRNA network to optimize their reproduction.

  • 1326.
    Zhao, Hongxing
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Konzer, Anne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mi, Jia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Chen, Moashan
    La Trobe University.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Lind, Sara Bergström
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Posttranscriptional regulation in adenovirus infected cells2017Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, nr 2, s. 872-888Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A deeper understanding of how viruses reprogramtheir hosts for production of progeny is needed to combatinfections. Most knowledge on the regulation of cellular geneexpression during adenovirus infection is derived from mRNAstudies. Here, we investigated the changes in protein expressionduring the late phase of adenovirus type 2 (Ad2) infection of theIMR-90 cell line by stable isotope labeling in cell culture withsubsequent liquid chromatography−high resolution tandemmass spectrometric analysis. Two biological replicates of samplescollected at 24 and 36 h post-infection (hpi) were investigated using swapped labeling. In total, 2648 and 2394 proteins werequantified at 24 and 36 hpi, respectively. Among them, 659 and 645 were deregulated >1.6-fold at the two time points. Theprotein expression was compared with RNA expression using cDNA sequencing data. The correlation was surprisingly low(r = 0.3), and several examples of posttranscriptional regulation were observed; e.g., proteins related to carbohydrate metabolismwere up-regulated at the protein level but unchanged at the RNA level, whereas histone proteins were down-regulated at theprotein level but up-regulated at the RNA level. The deregulation of cellular gene expression by adenovirus is mediated atmultiple levels and more complex than hitherto believed.

  • 1327.
    ZHAO, WENJUN
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Analysis of most common endogenous steroids in plasma2014Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 1328. Zhao, Xi
    et al.
    Wu, Jie
    Gong, Fang-Ling
    Cui, Jin-Mei
    Janson, Jan-Christer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Ma, Guang-Hui
    Su, Zhi-Guo
    Preparation of uniform and large sized agarose microspheres by an improved membrane emulsification technique2014Inngår i: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 253, s. 444-452Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The SPG (Shirasu porous-glass) membrane emulsification technique has been subject to much attention for the preparation of uniform emulsions. However, so far primarily used for the production of droplets with sizes below approximately 60 mu m. A production bottleneck occurred if the desired size was further increased, especially when highly viscous dispersed phases were involved. To this end, an improved membrane emulsification technique was proposed and has been applied to the preparation of large agarose microspheres, with a size of around 90 mu m and with a narrow size distribution. The effects of important emulsification parameters, including the pore size of the SPG membrane, the operating pressure, the stirring rate of the continuous phase, the composition of the continuous oil phase, and the concentration of agarose in the dispersed water phase, have been extensively studied. Under optimum conditions, uniform-size agarose microspheres with an average diameter of 93 pm and a size distribution index of 0.65 were successfully prepared. The average particle size of the home-made agarose microspheres was almost identical to that of the commercial product Sepharose 4 Fast Flow (4FF), which is produced by mechanical stirring and an additional sieving process. However, the size distribution of the former was much narrower than that of the latter. Therefore, the improved membrane emulsification technique presented here is promising for the application of high viscosity systems such as agarose solutions, and the production scale can be further enhanced by increasing the number of membrane units attached to the experimental apparatus. (C) 2013 Elsevier B.V. All rights reserved.

  • 1329.
    Zhou, Taigang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Asymmetric Hydrogenation of Functionalized Olefins Using N,P-Ligated Iridium Complexes2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Transition-metal-catalyzed asymmetric hydrogenation is one of the most efficient, straightforward, and well-established methods for preparing enantiomerically enriched compounds. Over the past decades, significant progress has been made with iridium, rhodium and ruthenium complexes to asymmetric hydrogenate a selection of olefins, such as, α,β-unsaturated carboxylic acid derivatives, ketones, imines and phosphonates. Although these metals have been applied successfully in the hydrogenation of olefins, they differ in their substrate tolerance.  Ruthenium and rhodium based catalysts require a coordinating group in the vicinity of the C=C bond. However, iridium based catalysts do not require this coordinating group, hence, asymmetric hydrogenation with iridium catalysts has been widely used for both functionalized and unfunctionalized olefin substrates. This thesis focuses on expanding the substrate scope for asymmetric hydrogenation using chiral N,P-ligated iridium catalysts. Papers I and II investigate the asymmetric hydrogenation of prochiral N-heterocyclic compounds prepared by ring-closing metathesis using the iridium catalysts developed in our group.  These substrates are interesting as they bear resemblance to pharmaceutically active compounds and therefore have tremendous value in medicinal chemistry.  Excellent enantioselectivities, up to >99% ee and conversions were obtained. In papers III and IV we synthesized many unsaturated acyclic and cyclic sulfones with varying substitution patterns.  The sulfones were subjected to hydrogenation using our N,P-ligated iridium catalysts, producing the chiral sulfone products in high enantiomeric excess (up to 99% ee). This methodology was combined with the Ramberg-Bäcklund reaction, offering a novel route to chiral allylic and homoallylic compounds. In addition to obtaining these chiral compounds in good yields, no decrease in enantiomeric excess was observed after the Ramberg-Bäcklund reaction. This strategy has been applied in the preparation of the chiral building block for renin inhibitors.

    Delarbeid
    1. Highly Flexible Synthesis of Chiral Azacycles via Iridium-Catalyzed Hydrogenation
    Åpne denne publikasjonen i ny fane eller vindu >>Highly Flexible Synthesis of Chiral Azacycles via Iridium-Catalyzed Hydrogenation
    Vise andre…
    2010 (engelsk)Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 132, nr 26, s. 8880-8881Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A range of saturated chiral azacycles has been prepared in high yield and with high selectivity from simple starting materials. A modular approach with ring-closing metathesis as a key step was used to produce a number of five-, six-, and seven-membered cyclic alkenes. Asymmetric hydrogenation catalyzed by N,P-ligated iridium complexes gave saturated azacycles in high optical purity. This methodology was demonstrated in the synthesis of a pharmaceutical precursor.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-135809 (URN)10.1021/ja103901e (DOI)000279561200033 ()20557052 (PubMedID)
    Tilgjengelig fra: 2010-12-09 Laget: 2010-12-08 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. Chiral Hetero- and Carbocyclic Compounds from the Asymmetric Hydrogenation of Cyclic Alkenes
    Åpne denne publikasjonen i ny fane eller vindu >>Chiral Hetero- and Carbocyclic Compounds from the Asymmetric Hydrogenation of Cyclic Alkenes
    Vise andre…
    2012 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, nr 21, s. 6507-6513Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Several types of chiral hetero- and carbocyclic compounds have been synthesized by using the asymmetric hydrogenation of cyclic alkenes. N,P-Ligated iridium catalysts reduced six-membered cyclic alkenes with various substituents and heterofunctionality in good to excellent enantioselectivity, whereas the reduction of five-membered cyclic alkenes was generally less selective, giving modest enantiomeric excesses. The stereoselectivity of the hydrogenation depended more strongly on the substrate structure for the five- rather than the six-membered cyclic alkenes. The major enantiomer formed in the reduction of six-membered alkenes could be predicted from a selectivity model and isomeric alkenes had complementary enantioselectivity, giving opposite optical isomers upon hydrogenation. The utility of the reaction was demonstrated by using it as a key step in the preparation of chiral 1,3-cis-cyclohexane carboxylates.

    Emneord
    asymmetric synthesis, heterocyclic compounds, homogeneous catalysis, hydrogenation, iridium
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-175620 (URN)10.1002/chem.201104073 (DOI)000304045000016 ()
    Tilgjengelig fra: 2012-06-12 Laget: 2012-06-11 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    3. Enantioselective Synthesis of Chiral Sulfones by Ir-Catalyzed Asymmetric Hydrogenation: A Facile Approach to the Preparation of Chiral Allylic and Homoallylic Compounds
    Åpne denne publikasjonen i ny fane eller vindu >>Enantioselective Synthesis of Chiral Sulfones by Ir-Catalyzed Asymmetric Hydrogenation: A Facile Approach to the Preparation of Chiral Allylic and Homoallylic Compounds
    Vise andre…
    2012 (engelsk)Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, nr 33, s. 13592-13595Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A highly efficient and enantioselective Ir-catalyzed hydrogenation of unsaturated sulfones was developed. Chiral cyclic and acyclic sulfones were produced in excellent enantioselectivities (up to 98% ee). Coupled with the Ramberg-Backlund rearrangement, this reaction offers a novel route to chiral allylic and homoallylic compounds in excellent enantioselectivities (up to 97% ee) and high yields (up to 94%).

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-182640 (URN)10.1021/ja306731u (DOI)000307699000016 ()
    Tilgjengelig fra: 2012-10-14 Laget: 2012-10-14 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    4. High Enantioselectivity of Chiral Sulfones byIridium Catalyzed Asymmetric Hydrogenation: An Efficient Access for Total Synthesis of Imperanene
    Åpne denne publikasjonen i ny fane eller vindu >>High Enantioselectivity of Chiral Sulfones byIridium Catalyzed Asymmetric Hydrogenation: An Efficient Access for Total Synthesis of Imperanene
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-182643 (URN)
    Tilgjengelig fra: 2012-10-14 Laget: 2012-10-14 Sist oppdatert: 2012-11-12
  • 1330.
    Zhou, Taigang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Peters, Byron
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Cadu, Alban
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Andersson, Pher
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    High Enantioselectivity of Chiral Sulfones byIridium Catalyzed Asymmetric Hydrogenation: An Efficient Access for Total Synthesis of ImperaneneManuskript (preprint) (Annet vitenskapelig)
  • 1331.
    Zhou, Taigang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Peters, Byron
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Maldonado, Matias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Govender, Thavendran
    Department of Pharmacy, University of KwaZulu-Natal.
    Andersson, Pher
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Enantioselective Synthesis of Chiral Sulfones by Ir-Catalyzed Asymmetric Hydrogenation: A Facile Approach to the Preparation of Chiral Allylic and Homoallylic Compounds2012Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, nr 33, s. 13592-13595Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A highly efficient and enantioselective Ir-catalyzed hydrogenation of unsaturated sulfones was developed. Chiral cyclic and acyclic sulfones were produced in excellent enantioselectivities (up to 98% ee). Coupled with the Ramberg-Backlund rearrangement, this reaction offers a novel route to chiral allylic and homoallylic compounds in excellent enantioselectivities (up to 97% ee) and high yields (up to 94%).

  • 1332.
    Zhou, Y.
    et al.
    Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, S-10405 Stockholm, Sweden..
    Bergsaker, H.
    Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, S-10405 Stockholm, Sweden..
    Bykov, I.
    Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, S-10405 Stockholm, Sweden..
    Petersson, P.
    Royal Inst Technol, Sch Elect Engn, Dept Fus Plasma Phys, S-10405 Stockholm, Sweden..
    Possnert, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, För teknisk-naturvetenskapliga fakulteten gemensamma enheter, Tandemlaboratoriet. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Tillämpad kärnfysik.
    Likonen, J.
    VTT Tech Res Ctr Finland, POB 1000, FIN-02044 Espoo, Finland..
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Culham Sci Ctr, CCFE, Abingdon OX14 3DB, Oxon, England..
    Koivuranta, S.
    VTT Tech Res Ctr Finland, POB 1000, FIN-02044 Espoo, Finland..
    Widdowson, A. M.
    Proceedings 25th IAEA Fus Energy Conf 2014, St Petersburg, Russia..
    Microanalysis of deposited layers in the inner divertor of JET with ITER-like wall2017Inngår i: NUCLEAR MATERIALS AND ENERGY, ISSN 2352-1791, Vol. 12, nr SI, s. 412-417Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In JET with ITER-like wall, beryllium eroded in the main chamber is transported to the divertor and deposited mainly at the horizontal surfaces of tiles 1 and 0 (high field gap closure, HFGC). These surfaces are tungsten coated carbon fibre composite (CFC). Surface sampleswere collected following the plasma operations in 2011-2012 and 2013-2014 respectively. The surfaces, as well as polished cross sections of the deposited layers at the surfaces have been studied with micro ion beam analysis methods (mu-IBA). Deposition of Beand other impurities, and retention of D is microscopically inhomogeneous. Impurities and trapped deuterium accumulate preferentially in cracks, pits and depressed regions, and at the sides of large pits in the substrate (e.g. arc tracks where the W coating has been removed). With careful overlaying of mu-NRA elemental maps with optical microscopy images, it is possible to separate surface roughness effects from depth profiles at microscopically flat surface regions.

  • 1333.
    Zhou, Yang
    et al.
    AlbaNova Univ Ctr, KTH Royal Inst Technol, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Zou, Rongfeng
    AlbaNova Univ Ctr, KTH Royal Inst Technol, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Kuang, Guanglin
    AlbaNova Univ Ctr, KTH Royal Inst Technol, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Halldin, Christer
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, S-17176 Stockholm, Sweden;Stockholm Cty Council, S-17176 Stockholm, Sweden.
    Ågren, Hans
    AlbaNova Univ Ctr, KTH Royal Inst Technol, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden;Henan Univ, Coll Chem & Chem Engn, Kaifeng 475004, Henan, Peoples R China.
    Tu, Yaoquan
    AlbaNova Univ Ctr, KTH Royal Inst Technol, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Enhanced Sampling Simulations of Ligand Unbinding Kinetics Controlled by Protein Conformational Changes2019Inngår i: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 59, nr 9, s. 3910-3918Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Understanding unbinding kinetics of protein-ligand systems is of great importance for the design of ligands with desired specificity and safety. In recent years, enhanced sampling techniques have emerged as effective tools for studying unbinding kinetics of protein-ligand systems at the atomistic level. However, in many protein-ligand systems, the ligand unbinding processes are strongly coupled to protein conformational changes and the disclosure of the hidden degrees of freedom closely related to the protein conformational changes so that sampling is enhanced over these degrees of freedom remains a great challenge. Here, we show how potential-scaled molecular dynamics (sMD) and infrequent metadynamics (InMetaD) simulation techniques can be combined to successfully reveal the unbinding mechanism of 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-[F-18]fluorodibenzo[b,d]thiophene 5,5-dioxide ([F-18]ASEM) from a chimera structure of the alpha 7-nicotinic acetylcholine receptor. By using sMD simulations, we disclosed that the "close to "open" conformational change of loop C plays a key role in the ASEM unbinding process. By carrying out InMetaD simulations with this conformational change taken into account as an additional collective variable, we further captured the key states in the unbinding process and clarified the unbinding mechanism of ASEM from the protein. Our work indicates that combining sMD and InMetaD simulation techniques can be an effective approach for revealing the unbinding mechanism of a protein-ligand system where protein conformational changes control the unbinding process.

  • 1334. Zhu, Bing
    et al.
    Trikudanathan, Subbulaxmi
    Zozulya, Alla L.
    Sandoval-Garcia, Carolina
    Kennedy, Jennifer K.
    Atochina, Olga
    Norberg, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Castagner, Bastien
    Seeberger, Peter
    Fabry, Zsuzsa
    Harn, Donald
    Khoury, Samia J.
    Guleria, Indira
    Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis2012Inngår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 142, nr 3, s. 351-361Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Parasitic infections frequently lead to immune deviation or suppression. However, the application of specific parasitic molecules in regulating autoimmune responses remains to be explored. Here we report on the immune modulatory function of Lacto-N-fucopentaose III (LNFPIII), a schistosome glycan, in an animal model for multiple sclerosis. We found that LNFPIII treatment significantly reduced the severity of experimental autoimmune encephalomyelitis (EAE) and CNS inflammation, and skewed peripheral immune response to a Th2 dominant profile. Inflammatory monocytes (IMCs) purified from LNFPIII-treated mice had increased expression of nitric oxide synthase 2, and mediated T cell suppression. LNFPIII treatment also significantly increased mRNA expression of arginase-1, aldehyde dehydrogenase 1 subfamily A2, indoleamine 2,3-dioxygenase and heme oxygenase 1 in splenic IMCs. Furthermore, LNFPIII treatment significantly reduced trafficking of dendritic cells across brain endothelium in vitro. In summary, our study demonstrates that LNFPIII glycan treatment suppresses EAE by modulating both innate and T cell immune response.

  • 1335. Zhu, Bing
    et al.
    Trikudanathan, Subbulaxmi
    Zozulya, Alla L
    Sandoval-Garcia, Carolina
    Kennedy, Jennifer K
    Atochina, Olga
    Norberg, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Castagner, Bastien
    Seeberger, Peter
    Fabry, Zsuzsa
    Harn, Donald
    Khoury, Samia J
    Guleria, Indira
    Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis2012Inngår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 142, nr 3, s. 351-361Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Parasitic infections frequently lead to immune deviation or suppression. However, the application of specific parasitic molecules in regulating autoimmune responses remains to be explored. Here we report on the immune modulatory function of Lacto-N-fucopentaose III (LNFPIII), a schistosome glycan, in an animal model for multiple sclerosis. We found that LNFPIII treatment significantly reduced the severity of experimental autoimmune encephalomyelitis (EAE) and CNS inflammation, and skewed peripheral immune response to a Th2 dominant profile. Inflammatory monocytes (IMCs) purified from LNFPIII-treated mice had increased expression of nitric oxide synthase 2, and mediated T cell suppression. LNFPIII treatment also significantly increasedmRNA expression of arginase-1, aldehyde dehydrogenase 1 subfamily A2, indoleamine 2,3-dioxygenase and heme oxygenase 1 in splenic IMCs. Furthermore, LNFPIII treatment significantly reduced trafficking of dendritic cells across brain endothelium in vitro

    . In summary, our study demonstrates that LNFPIII glycan treatment suppresses EAE by modulating both innate and T cell immune response.

  • 1336.
    Zhu, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Fogarty, Heather A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Mollerstedt, Helene
    Brink, Maria
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Aromaticity Effects on the Profiles of the Lowest Triplet-State Potential-Energy Surfaces for Rotation about the CC Bonds of Olefins with Five-Membered Ring Substituents: An Example of the Impact of Baird's Rule2013Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, nr 32, s. 10698-10707Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A density functional theory study on olefins with five-membered monocyclic 4n and 4n+2 -electron substituents (C4H3X; X=CH+, SiH+, BH, AlH, CH2, SiH2, O, S, NH, and CH-) was performed to assess the connection between the degree of substituent (anti)aromaticity and the profile of the lowest triplet-state ( (1)) potential-energy surface (PES) for twisting about olefinic CC bonds. It exploited both Huckel's rule on aromaticity in the closed-shell singlet ground state (S-0) and Baird's rule on aromaticity in the lowest * excited triplet state. 2CH(C4H3X) were categorized as set A and set B olefins depending on which carbon atom (C2 or C3) of the C4H3X ring is bonded to the olefin. (0)-antiaromatic/ (1)-aromatic (C5H4+) to strongly S-0-aromatic/ (1)- antiaromatic (C5H4-). Our hypothesis is that the shapes of the (1) PESs, as given by the energy differences between planar and perpendicularly twisted olefin structures in (1) [E( (1))], smoothly follow the changes in substituent (anti)aromaticity. Indeed, correlations between E( (1)) and the (anti)aromaticity changes of the C4H3X groups, as measured by the zz-tensor component of the nucleus-independent chemical shift NICS( (1);1)(zz), are found both for sets A and B separately (linear fits; r(2)=0.949 and 0.851, respectively) and for the two sets combined (linear fit; r(2)=0.851). For sets A and B combined, strong correlations are also found between E( (1)) and the degree of S-0 (anti)aromaticity as determined by NICS(S-0,1)(zz) (sigmoidal fit; r(2)=0.963), as well as between the (1) energies of the planar olefins and NICS(S-0,1)(zz) (linear fit; r(2)=0.939). (1) PESs suitable for adiabatic Z/E photoisomerization.

  • 1337.
    Zhu, Jun
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Tong, Hui
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Rosenberg, Martin
    Jahn, Burkhard O.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Kilsa, Kristine
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Baird's rule on excited state (anti)aromaticity as a tool for rationalization of photophysical and photochemical properties and processes2013Inngår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 245, s. 755-ORGN-Artikkel i tidsskrift (Annet vitenskapelig)
  • 1338.
    Zhu, Yanping
    et al.
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Qi, Xiaoying
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Yu, Cuicui
    Qing Dao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Anesthesiol, 20 Yudong Rd, Yantai S264009, Shandong, Peoples R China.
    Yu, Shoujun
    Binzhou Med Univ, Yantai Affiliated Hosp, Dept Ultrasound, 717 Jinfu Rd, Binzhou 264100, Shandong, Peoples R China.
    Zhang, Chao
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Zhang, Yuan
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Liu, Xiuxiu
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Xu, Yuxue
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Yang, Chunhua
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Jiang, Wenguo
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Tian, Geng
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Li, Xuri
    Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Zhang, Jiandi
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China;Yantai Zestern Biotech Co LTD, 39 Keji Ave Bioasis, Yantai, Peoples R China.
    Wang, Lei
    Harbin Med Univ, Affiliated Hosp 1, Dept Thorac Surg, 23 Youzheng St, Harbin 150000, Heilongjiang, Peoples R China.
    Mi, Jia
    Binzhou Med Univ, Precis Med Res Ctr, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China.
    Identification of prothymosin alpha (PTMA) as a biomarker for esophageal squamous cell carcinoma (ESCC) by label-free quantitative proteomics and Quantitative Dot Blot (QDB)2019Inngår i: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 16, artikkel-id 12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Esophageal cancer (EC) is one of the malignant tumors with a poor prognosis. The early stage of EC is asymptomatic, so identification of cancer biomarkers is important for early detection and clinical practice.

    Methods: In this study, we compared the protein expression profiles in esophageal squamous cell carcinoma (ESCC) tissues and adjacent normal esophageal tissues from five patients through high-resolution label-free mass spectrometry. Through bioinformatics analysis, we found the differentially expressed proteins of ESCC. To perform the rapid identification of biomarkers, we adopted a high-throughput protein identification technique of Quantitative Dot Blot (QDB). Meanwhile, the QDB results were verified by classical immunohistochemistry.

    Results: In total 2297 proteins were identified, out of which 308 proteins were differentially expressed between ESCC tissues and normal tissues. By bioinformatics analysis, the four up-regulated proteins (PTMA, PAK2, PPP1CA, HMGB2) and the five down-regulated proteins (Caveolin, Integrin beta-1, Collagen alpha-2(VI), Leiomodin-1 and Vinculin) were selected and validated in ESCC by Western Blot. Furthermore, we performed the QDB and IHC analysis in 64 patients and 117 patients, respectively. The PTMA expression was up-regulated gradually along the progression of ESCC, and the PTMA expression ratio between tumor and adjacent normal tissue was significantly increased along with the progression. Therefore, we suggest that PTMA might be a potential candidate biomarker for ESCC.

    Conclusion: In this study, label-free quantitative proteomics combined with QDB revealed that PTMA expression was up-regulated in ESCC tissues, and PTMA might be a potential candidate for ESCC. Since Western Blot cannot achieve rapid and high-throughput screening of mass spectrometry results, the emergence of QDB meets this demand and provides an effective method for the identification of biomarkers.

  • 1339.
    Zoerner, Frank
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lennmyr, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Martijn, Cécile
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Semenas, Egidijus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrestManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Long-term survival after cardiac arrest (CA) due to shock-refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets.

    Methods: Twenty-six immature male piglets were subjected to 12 min VF followed by 8 min CPR. The treatment group (n=13) received i.v. boluses vasopressin 0.4 U∙kg−1, esmolol 250 μg∙kg−1 and milrinone 25 μg∙kg−1 after 13 min, followed by i.v. boluses esmolol 375 μg∙kg−1 and milrinone 25 μg∙kg−1 after 18 min and continuous esmolol 15 μg∙kg−1∙h−1 infusion during 180 min reperfusion, while controls (n=13) received equal amounts of vasopressin and saline. A 200J monophasic counter-shock was delivered to achieve resumption of spontaneous circulation (ROSC) after 8 min CPR. If ROSC was not achieved, another 200J defibrillation and bolus vasopressin 0.4 U∙kg−1 were administered in both groups. DC shocks at 360J were applied as one shot min−1 over maximally 5 min. Hemodynamic variables and troponin I as a marker of cardiac injury were recorded.

    Results: Troponin I levels after 180 min reperfusion were lower in the treatment group than in controls (p<0.05). The treatment group received less norepinephrine (p<0.01) and had greater diuresis (p<0.01). There was no difference in survival between groups.

    Conclusions: The combination of milrinone, esmolol and vasopressin decreased cardiac injury compared with vasopressin alone. 

  • 1340.
    Zoerner, Frank
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lennmyr, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Martijn, Cécile
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Semenas, Egidijus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest2015Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 4, s. 465-474Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Long-term survival after cardiac arrest (CA) due to shock-refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets.

    METHODS: A total of 26 immature male piglets were subjected to 12-min VF followed by 8-min CPR. The treatment group (n = 13) received i.v. (intravenous) boluses vasopressin 0.4 U/kg, esmolol 250 μg/kg and milrinone 25 μg/kg after 13 min, followed by i.v. boluses esmolol 375 μg/kg and milrinone 25 μg/kg after 18 min and continuous esmolol 15 μg/kg/h infusion during 180 min reperfusion, whereas controls (n = 13) received equal amounts of vasopressin and saline. A 200 J monophasic counter-shock was delivered to achieve resumption of spontaneous circulation (ROSC) after 8 min CPR. If ROSC was not achieved, another 200 J defibrillation and bolus vasopressin 0.4 U/kg would be administered in both groups. Direct current shocks at 360 J were applied as one shot per minute over maximally 5 min. Hemodynamic variables and troponin I as a marker of cardiac injury were recorded.

    RESULTS: Troponin I levels after 180 min reperfusion were lower in the treatment group than in controls (P < 0.05). The treatment group received less norepinephrine (P < 0.01) and had greater diuresis (P < 0.01). There was no difference in survival between groups.

    CONCLUSION: The combination of milrinone, esmolol and vasopressin decreased cardiac injury compared with vasopressin alone.

  • 1341.
    Zoerner, Frank
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Miclescu, Adriana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Martijn, Cecile
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Therapeutic hypothermia activates the endothelin and nitric oxide systems after cardiac arrest in a pig model of cardiopulmonary resuscitation2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 5, s. e64792-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Post-cardiac arrest myocardial dysfunction is a major cause of mortality in patients receiving successful cardiopulmonary resuscitation (CPR). Mild therapeutic hypothermia (MTH) is the recommended treatment after resuscitation from cardiac arrest (CA) and is known to exert neuroprotective effects and improve short-term survival. Yet its cytoprotective mechanisms are not fully understood. In this study, our aim was to determine the possible effect of MTH on vasoactive mediators belonging to the endothelin/nitric oxide axis in our porcine model of CA and CPR. Pigs underwent either untreated CA or CA with subsequent CPR. After state-of-the-art resuscitation, the animals were either left untreated, cooled between 32-34°C after ROSC or treated with a bolus injection of S-PBN (sodium 4-[(tert-butylimino) methyl]benzene-3-sulfonate N-oxide) until 180 min after ROSC, respectively. The expression of endothelin 1 (ET-1), endothelin converting enzyme 1 (ECE-1), and endothelin A and B receptors (ETAR and ETBR) transcripts were measured using quantitative real-time PCR while protein levels for the ETAR, ETBR and nitric oxide synthases (NOS) were assessed using immunohistochemistry and Western Blot. Our results indicated that the endothelin system was not upregulated at 30, 60 and 180 min after ROSC in untreated postcardiac arrest syndrome. Post-resuscitative 3 hour-long treatments either with MTH or S-PBN stimulated ET-1, ECE-1, ETAR and ETBR as well as neuronal NOS and endothelial NOS in left ventricular cardiomyocytes. Our data suggests that the endothelin and nitric oxide pathways are activated by MTH in the heart.

  • 1342.
    Zou, Rongfeng
    et al.
    AlbaNova Univ Ctr, Royal Inst Technol KTH, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Kuang, Guanglin
    AlbaNova Univ Ctr, Royal Inst Technol KTH, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Ågren, Hans
    AlbaNova Univ Ctr, Royal Inst Technol KTH, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden;Henan Univ, Coll Chem & Chem Engn, Kaifeng 475004, Henan, Peoples R China.
    Nordberg, Agneta
    Karolinska Univ Hosp, Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,Clin Geriatr Neo & Theme Aging, S-14183 Huddinge, Sweden.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Tu, Yaoquan
    AlbaNova Univ Ctr, Royal Inst Technol KTH, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.
    Free Energy Profile for Penetration of Pittsburgh Compound-B into the Amyloid β Fibril2019Inngår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, nr 3, s. 1783-1790Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The amyloid β (Aβ) fibril is a hallmark of Alzheimer's disease (AD) and has therefore served as an important target for early diagnosis of AD. The Pittsburgh Compound-B (PiB) is one of the most famous positron emission tomography (PET) tracers commonly used for in vivo detection of Aβ fibrils. Many theoretical studies have predicted the existence of various core binding sites with different microenvironments for probes binding to the Aβ fibril. However, little attention has been devoted to how the probes actually penetrate into the different core binding sites. In this study, an integrated molecular modeling scheme is used to study the penetration of PiB into the core binding sites of the Aβ1-42 fibril structure recently obtained by cryogenic electron microscopy. We find that there are two core binding sites for PiB with dramatic differences in cavity size and microenvironment properties, and furthermore that the penetration of PiB into site-1 is energetically prohibitive, whereas the penetration into site 2 is much more favorable. Therefore, the binding capacity at site-2 may be larger than that at site-1 despite its lower binding affinity. Our results thus suggest that site-2 may be a major binding site for PiB binding to Aβ fibril and emphasize the importance to adopt a full dynamical picture when studying tracer fibril binding problems in general, something that in turn can be used to guide the development of tracers with higher affinity and selectivity for the Aβ fibril.

  • 1343.
    Åberg, Ola
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Combinatorial synthesis of labelled drugs and PET tracers: synthesis of a focused library of 11C-carbonyl-labelled acrylamides as potential biomarkers of EGFR expression2012Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 55, nr 14, s. 477-483Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Combinatorial synthesis is extensively used in drug development and lead optimisation. However, this approach has rarely been used for positron emission tomography because of limitations in available technologies. [11C]Carbon monoxide is amenable to combinatorial synthesis in transition-metal-catalysed reactions because it can react with a wide variety of electrophiles and nucleophiles, which opens up the possibilities for combinatorial radiochemistry. Herein, we exemplify the combinatorial approach by 11C-labelling a library of epidermal growth factor receptor inhibitors. The selection of candidates was guided by molecular docking. Epidermal growth factor receptor is overexpressed in a variety of tumours, and it has become an important drug target. The 11C-labelling reactions were performed using four substituted vinyl iodides and three different 4-anilino-6-aminoquinazolines using a palladium-mediated reaction with [11C]carbon monoxide using a single set of reaction conditions. In total, 12 labelled acrylamide derivatives were radiolabelled and obtained in 24–61% decay-corrected radiochemical yield (from [11C]carbon monoxide). Starting from 5.6 GBq [11C]carbon monoxide, 0.85 GBq of formulated N-[4-(3-bromo-phenylamino)-quinazolin-6-yl]-acryl[11C]amide [11C]12da was obtained within 47 min from end of bombardment (specific activity of 60 GBq µmol−1). This strategy is an example of how [11C]carbon monoxide can be utilised in the labelling of libraries of drug candidates and positron emission tomography tracers for in vitro and in vivo testing.

  • 1344.
    Åkerlund, Lisa
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Emanuelsson, Rikard
    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.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Quinone based Conducting Redox Polymers for Renewable Energy Storage2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    To meet future energy needs and to minimize CO2-emissions, a higher share of produced electricity must come from renewable resources [1]. Unfortunately, the output of renewable energy sources varies and does not always correlate with the temporal demand for electricity. For this reason, high capacity electrical energy storage (EES) is needed to fully utilize renewable energy sources [2]. Today’s battery technologies primarily rely on metals extracted at large economic and environmental costs [3],and the benefits of converting to carbon based materials are several, e.g. lower weight, flexible materials, and better recycling possibilities. In addition, the total energy consumption in the production chain may be reduced if the high temperatures required for extracting and processing metals can be avoided. Conducting redox polymers (CRPs), i.e. conducting polymers with redox active side groups, are currently investigated as possible organic electrode materials [4]. In this work we focus on finding stable side groups with high charge storage capacity. Quinones, which occur in natural energy conversion systems, i.e. during photosynthesis and respiration, are an attractive side group for CRPs due to their high gravimetric capacity. Importantly, for a functioning battery application the redox group and the polymer backbone must be active in the same potential window and this can be tuned effectively over a wide potential range by substitution on the quinone ring; hence various quinone derivatives could match different polymer backbones. A high potential- and high charge capacity quinone derivative has been synthesized and electrochemically characterized with the aim of producing a novel CRP to function as an organic high charge capacity material, targeting renewable organic batteries for a future of sustainable EES.

     

    References

    [1]  D. Larcher, J. M. Tarascon,, Nat. Chem. 7 (2015) 19-29.

    [2] Z. Yang, J. Zhang, M. C. W. Kintner-Meyer, X. Lu, D. Choi, J. P. Lemmon, J. Liu, Chem. Rev. 111 (2011) 3577–3613.

    [3] P. Poizot, F. Dolhem, Energy Environ. Sci. 4 (2011) 2003-2019.

    [4] (a) C. Karlsson, H. Huang, M. Stromme, A. Gogoll, M. Sjodin, RSC Adv. 5 (2015) 11309-11316; (b) C. Karlsson, H. Huang, M. Stromme, A. Gogoll, M. Sjodin, Electrochim. Acta 179 (2015) 336-342.

    [5] L. Åkerlund, R. Emanuelsson, A. Gogoll, M. Strömme, M. Sjödin, To be submitted.

  • 1345.
    Åkerlund, Lisa
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Emanuelsson, Rikard
    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.
    Strømme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Organic Materials for Renewable Energy Storage2016Konferansepaper (Fagfellevurdert)
  • 1346.
    Åkerlund, Lisa
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Emanuelsson, Rikard
    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.
    Strømme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Sjödin, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Quinone based Conducting Redox Polymers for Renewable Energy Storage2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    To meet future energy needs and to minimize CO2-emissions, a higher share of produced electricity must come from renewable resources [1]. Unfortunately, the output of renewable energy sources varies and does not always correlate with the temporal demand for electricity. For this reason, high capacity electrical energy storage (EES) is needed to fully utilize renewable energy sources [2]. Today’s battery technologies primarily rely on metals extracted at large economic and environmental costs [3],and the benefits of converting to carbon based materials are several, e.g. lower weight, flexible materials, and better recycling possibilities. In addition, the total energy consumption in the production chain may be reduced if the high temperatures required for extracting and processing metals can be avoided. Conducting redox polymers (CRPs), i.e. conducting polymers with redox active side groups, are currently investigated as possible organic electrode materials [4]. In this work we focus on finding stable side groups with high charge storage capacity. Quinones, which occur in natural energy conversion systems, i.e. during photosynthesis and respiration, are an attractive side group for CRPs due to their high gravimetric capacity. Importantly, for a functioning battery application the redox group and the polymer backbone must be active in the same potential window and this can be tuned effectively over a wide potential range by substitution on the quinone ring; hence various quinone derivatives could match different polymer backbones. A high potential- and high charge capacity quinone derivative has been synthesized and electrochemically characterized with the aim of producing a novel CRP to function as an organic high charge capacity material, targeting renewable organic batteries for a future of sustainable EES.

     

    References

    [1]  D. Larcher, J. M. Tarascon,, Nat. Chem. 7 (2015) 19-29.

    [2] Z. Yang, J. Zhang, M. C. W. Kintner-Meyer, X. Lu, D. Choi, J. P. Lemmon, J. Liu, Chem. Rev. 111 (2011) 3577–3613.

    [3] P. Poizot, F. Dolhem, Energy Environ. Sci. 4 (2011) 2003-2019.

    [4] (a) C. Karlsson, H. Huang, M. Stromme, A. Gogoll, M. Sjodin, RSC Adv. 5 (2015) 11309-11316; (b) C. Karlsson, H. Huang, M. Stromme, A. Gogoll, M. Sjodin, Electrochim. Acta 179 (2015) 336-342.

    [5] L. Åkerlund, R. Emanuelsson, A. Gogoll, M. Strömme, M. Sjödin, To be submitted.

  • 1347.
    Ålander, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Kinetic studies of serine protease inhibitors in 'active barrier' model systems2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 1348.
    Östlund, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Influence of pH on the size and shape of micellesformed by an amphiphilic drug in normal salinitystudied with static and dynamic light scattering2019Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 1349.
    Ślósarczyk, Adam T.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Baltzer, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Efficient formation of heterodimers from peptides and proteins using unsymmetrical polyfluorophenyl esters of dicarboxylic acids2012Inngår i: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 18, nr 4, s. 261-269Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An efficient method for the heteroconjugation of biomolecules carrying free amino groups was reported previously, where mixed polyfluorophenyl diesters of dicarboxylic acids with varied aliphatic chain length were shown to be efficient reagents for the conjugation of a variety of model biomolecules. The concept was based on the differential reactivity of the esters towards amines. The concept has now been further optimized, and a 2,6-difluorophenyl-pentafluorophenyl diester combination has been demonstrated to be the most efficient, both with respect to selectivity and to reaction rate. A pentafluorophenyl ester reacts faster with an amino group and requires a weaker base than a 2,6-difluorophenyl ester that requires a stronger base and longer reaction time. With the use of this combination of esters, we obtained considerably shortened reaction times compared with those reported previously, yet still retaining the desired selectivity in heteroconjugation. The increased reactivity of the bifunctional reagent allowed the construction of sophisticated peptide heteroconjugates from peptides, carbohydrates and proteins, showing a wide scope of applicability in the field of assembling functional bioconjugates.

  • 1350.
    Ślósarczyk, Adam T.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Ramapanicker, Ramesh
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Norberg, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Baltzer, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Mixed pentafluorophenyl and o-fluorophenyl esters of aliphatic dicarboxylic acids: efficient tools for peptide and protein conjugation2012Inngår i: RSC Advances, ISSN 2046-2069, Vol. 2, nr 3, s. 908-914Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An efficient methodology for the heteroconjugation of biomolecules with exposed free amino groups has been developed. Mixed pentafluorophenyl and o-fluorophenyl esters of aliphatic dicarboxylic acids with aliphatic chains of varying sizes have been prepared and used to conjugate a 42-residue polypeptides with short model peptides as well as a model dodecapeptide with the antigenic determinant of type B blood, a carbohydrate derivative, to form a glycopeptide. The concept is based on the difference in reactivity towards primary amino groups between phenyl esters with leaving groups of unlike pKa. The reactivities of several pentafluorophenyl and o-fluorophenyl esters towards amino groups were carefully determined under reaction conditions to identify leaving group combinations that would provide optimal differences in reactivity for maximum yields of heteroconjugate formation while keeping the reasonable reaction times. Pentafluorophenyl esters react faster with an amino group and require a weaker base, while an o-fluorophenyl ester requires a stronger base and longer reaction time. The method described is economic, quick and gives complete control over the conjugation reaction. The size of the spacer is conveniently varied by selection of the appropriate aliphatic dicarboxylic acid. While the presented examples describe conjugation reactions of polypeptides with a maximum of 42 residues it is envisioned that the bifunctional linkers reported here will find their most important applications in the heteroconjugation of proteins using lysine side chains, a reaction for which currently few alternatives exist, if access to spacers of variable size is required.

24252627 1301 - 1350 of 1350
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