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  • 151.
    Bodvik, Rasmus
    et al.
    KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, Sweden.
    Karlson, Lief
    Akzo Nobel Functional Chemicals AB, Sweden.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Thormann, Esben
    KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, Sweden.
    Claesson, Per Martin
    FRIAS, School of Soft Matter Research, University of Freiburg, Germany AND KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, Sweden.
    Aggregation of modified celluloses in aqueous solution: transition from methylcellulose to hydroxypropylmethylcellulose solution properties induced by a low molecular weight oxyethylene additive2012Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 28, nr 38, s. 13562-13569Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Temperature effects on viscosity and aggregation behaviour of aqueous solutions of three different cellulose ethers: methylcellulose (MC), hydroxypropylmethylcellulose (HPMC) and ethyl(hydroxyethyl)cellulose (EHEC), were investigated using viscosity and dynamic light scattering measurements as well as Cryo-TEM. In all cases increasing temperature reduces the solvent quality of water, which induces aggregation. It was found that the aggregation rate followed the order EHEC > HPMC > MC, suggesting that cellulose ethers containing some bulky and partly hydrophilic substituents assemble into large aggregates more readly than methylcellulose. This finding is discussed in terms of the organization of the structures formed by the different cellulose ethers. The temperature-dependent association behavior of cellulose ethers was also investigated in a novel way by adding diethyleneglycolmonobutylether (BDG) to methylcellulose aqueous solutions. When the concentration of BDG was at and above 5 wt%, methylcellulose adopted HPMC-like solution behaviour. In particular, a transition temperature where the viscosity was decreasing, prior to increasing at higher temperatures, appeared and the aggregation rate increased. This observation is rationalized by the ability of the amphiphilic BDG to accumulate at non-polar interfaces, and thus also to associate with hydrophobic regions of methylcellulose. In effect BDG is suggested to act as a physisorbed hydrophilic and bulky substituent inducing similar constraints on aggregation as the chemically attached hydroxypropyl groups in HPMC and oligo(ethyleneoxide) chains in EHEC.

  • 152. Boge, Lucas
    et al.
    Bysell, Helena
    Ringstad, Lovisa
    Wennman, David
    Umerska, Anita
    Cassisa, Viviane
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Joly-Guillou, Marie-Laure
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Andersson, Martin
    Lipid-Based Liquid Crystals As Carriers for Antimicrobial Peptides: Phase Behavior and Antimicrobial Effect2016Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 32, nr 17, s. 4217-4228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, zeta-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

  • 153. Boge, Lukas
    et al.
    Umerska, Anita
    Matougui, Nada
    Bysell, Helena
    Ringstad, Lovisa
    Davoudi, Mina
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Andersson, Martin
    Cubosomes post-loaded with antimicrobial peptides: characterization, bactericidal effect and proteolytic stability.2017Inngår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 526, nr 1-2, s. 400-412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Novel antibiotics, such as antimicrobial peptides (AMPs), have recently attended more and more attraction. In this work, dispersed cubic liquid crystalline gel (cubosomes) was used as drug delivery vehicles for three AMPs (AP114, DPK-060 and LL-37). Association of peptides onto cubosomes was studied at two cubosome/peptide ratios using high performance liquid chromatography, ζ-potential and circular dichroism measurements. AMPs impact on the cubosome structure was investigated using small angle x-ray scattering and cryogenic transmission electron microscopy. The antimicrobial effect of the AMP loaded cubosomes was studied in vitro by minimum inhibitory concentration and time-kill assays. Proteolytic protection was investigated by incubating the formulations with two elastases and the antimicrobial effect after proteolysis was studied using radial diffusion assay. Different association efficacy onto the cubosomes was observed among the AMPs, with LL-37 showing greatest association (>60%). AP114 loaded cubosomes displayed a preserved antimicrobial effect, whereas for LL-37 the broad spectrum bacterial killing was reduced to only comprise Gram-negative bacteria. Interestingly, DPK-060 loaded cubosomes showed a slight enhanced effect against S. aureus and E. coli strains. Moreover, the cubosomes were found to protect LL-37 from proteolytic degradation, resulting in a significantly better bactericidal effect after being subjected to elastase, compared to unformulated peptide.

  • 154.
    Boge, Lukas
    et al.
    RISE Res Inst Sweden, Div Biosci & Mat, Stockholm, Sweden; Chalmers Univ Technol, Chem & Chem Engn, Gothenburg, Sweden.
    Umerska, Anita
    MINT Univ Angers, Angers, France.
    Matougui, Nada
    MINT Univ Angers, Angers, France.
    Bysell, Helena
    RISE Res Inst Sweden, Div Biosci & Mat, Stockholm, Sweden.
    Ringstad, Lovisa
    RISE Res Inst Sweden, Div Biosci & Mat, Stockholm, Sweden.
    Davoudi, Mina
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Andersson, Martin
    Chalmers Univ Technol, Chem & Chem Engn, Gothenburg, Sweden.
    Liquid crystalline particles for delivery of antimicrobial peptides2018Inngår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Artikkel i tidsskrift (Annet vitenskapelig)
  • 155. Boge, Lukas
    et al.
    Västberg, Amanda
    Umerska, Anita
    Bysell, Helena
    Eriksson, Jonny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Millqvist-Fureby, Anna
    Andersson, Martin
    Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide2018Inngår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 522, s. 126-135Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Liquid crystalline nanoparticles (LCNPs), e.g. cubosomes and hexosomes, are receiving more and more attraction as drug delivery vehicles. Dry powder formulation that forms LCNPs upon hydration can be advantageous to make new routes of administration accessible. In this work, we investigate use of three disaccharides (lactose, trehalose and sucrose) as protective matrices for glycerol monooleate based LCNP forming powders produced by freeze-drying. Phase behavior, particle size and size distributions at the different preparation steps were monitored by small angle x-ray scattering (SAXS) and dynamic light scattering (DLS). Particle appearance was imaged by cryogenic transmission electron microscopy (cryo-TEM). Moreover, the therapeutic relevant antimicrobial peptide AP114 (plectasin derivative) was incorporated in the formulations. Peptide encapsulation and release as well as in vitro antibacterial effect were investigated. Results showed that all freeze-dried powders did form particles with liquid crystalline structure upon hydration. However, a phase transition from the bicontinuous cubic Pn3m to the reversed hexagonal was observed, as a consequence of sugar addition and the freeze-drying procedure. Data indicates that trehalose is the preferred choice of lyo-protectant in order to maintain a mono-modal particle size distribution. In addition, antimicrobial activity of AP114-containing formulations was found to be highest for the formulation containing trehalose. The release kinetics of AP114 from the nanoparticles was strongly affected by the dimensions of the hexagonal phase. Larger dimension of the hexagonal phase, significantly improved the release of AP114 and antimicrobial activity of the formulation.

  • 156. Bonnet, Cecilia
    et al.
    Rusz, Jan
    Megrelishvili, Marika
    Sieger, Tomas
    Matouskova, Olga
    Okujava, Michael
    Brozova, Hana
    Nikolai, Tomas
    Hanuska, Jaromir
    Kapianidze, Mariam
    Mikeladze, Nina
    Botchorishvili, Nazi
    Khatiashvili, Irine
    Janelidze, Marina
    Serranova, Tereza
    Fiala, Ondrej
    Roth, Jan
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Jech, Robert
    Rivaud-Pechoux, Sophie
    Gaymard, Bertrand
    Ruzicka, Evzen
    Eye Movements in Ephedrone-Induced Parkinsonism2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e104784-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinson's disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro-and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese-induced damage to the basal ganglia, reflecting their role in oculomotor system.

  • 157.
    Borbas, Eszter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Synthesis and characterization of lanthanide-tetrapyrrole dyads2014Inngår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 248Artikkel i tidsskrift (Annet vitenskapelig)
  • 158.
    Botling Taube, Amelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Konzer, Anne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Alm, Albert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Oftalmiatrik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Proteomic Analysis of the Aqueous Humor in Eyes with Pseudoexfoliation SyndromeArtikkel i tidsskrift (Fagfellevurdert)
  • 159.
    Botling Taube, Amelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Karolinska Inst, Dept Clin Neurosci, St Erik Eye Hosp, Stockholm, Sweden.
    Konzer, Anne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Alm, Albert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Proteomic analysis of the aqueous humour in eyes with pseudoexfoliation syndrome2019Inngår i: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 103, nr 8, s. 1190-1194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/aims Pseudoexfoliation syndrome (PEX) is characterised by the production and accumulation of extracellular fibrillar material in the anterior segment of the eye. The pathogenesis of PEX is multifactorial with genetic factors and ageing as contributing factors. Previously, an increased concentration of beta-crystalline B2 (CRYBB2) was observed in the aqueous humour (AH) in eyes with PEX in a pooled material. Here, the protein content was examined on individual basis. Methods During cataract surgery, AH was sampled from patients with and without PEX, 10 eyes in each group. The proteins were digested and labelled with isotopomeric dimethyl labels, separated with high-pressure liquid chromatography and analysed in an Orbitrap mass analyzer. Results The concentration of complement factor 3, kininogen-1, antithrombin III and vitamin D-binding protein was increased in all eyes with PEX. Retinol-binding protein 3, glutathione peroxidase, calsyntenin-1 and carboxypeptidase E were decreased in eyes with PEX. Beta-crystalline B1 and CRYBB2 and gamma-crystalline D were up to eightfold upregulated in 4 of 10 in eyes with PEX. Conclusion The results indicate that oxidative stress and inflammation are contributing factors in the formation of PEX. Knowledge about the proteome in PEX is relevant for understanding this condition.

  • 160.
    Botling Taube, Amelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. 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.
    Alm, Albert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Oftalmiatrik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Imaging of Human Lens Capsules with Pseudoexfoliation Syndrome by Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS)Manuskript (preprint) (Annet vitenskapelig)
  • 161.
    Bowden, John A.
    et al.
    NIST, Marine Biochem Sci Grp, Div Chem Sci, Hollings Marine Lab, Charleston, SC 29412 USA..
    Heckert, Alan
    NIST, Stat Engn Div, Gaithersburg, MD 20899 USA..
    Ulmer, Candice Z.
    NIST, Marine Biochem Sci Grp, Div Chem Sci, Hollings Marine Lab, Charleston, SC 29412 USA..
    Jones, Christina M.
    NIST, Marine Biochem Sci Grp, Div Chem Sci, Hollings Marine Lab, Charleston, SC 29412 USA..
    Koelmel, Jeremy P.
    Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA..
    Abdullah, Laila
    Roskamp Inst, Sarasota, FL USA..
    Ahonen, Linda
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark..
    Alnouti, Yazen
    Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE USA..
    Armando, Aaron M.
    Univ Calif San Diego, Sch Med, Dept Chem & Biochem, La Jolla, CA 92093 USA.;Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA..
    Asara, John M.
    Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Bamba, Takeshi
    Kyushu Univ, Med Inst Bioregulat, Res Ctr Trans Med, Div Metabol,Higashi Ku, Fukuoka, Japan..
    Barr, John R.
    Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Div Lab Sci, Atlanta, GA USA..
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Borchers, Christoph H.
    Univ Victoria, Genome British Columbia Prote Ctr, Victoria, BC, Canada.;Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada.;McGill Univ, Jewish Gen Hosp, Gerald Bronfman Dept Oncol, Montreal, PQ, Canada.;McGill Univ, Jewish Gen Hosp, Prote Ctr, Segal Canc Ctr,Lady Davis Inst, Montreal, PQ, Canada..
    Brandsma, Joost
    Univ Southampton, Southampton Gen Hosp, Acad Unit Clin & Expt Sci, Fac Med, Southampton, Hants, England..
    Breitkopf, Susanne B.
    Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA..
    Cajka, Tomas
    Univ Calif Davis, Genome Ctr, Natl Inst Hlth West Coast Metabol Ctr, Davis, CA 95616 USA..
    Cazenave-Gassiot, Amaury
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore.;Singapore Lipidomic Incubator SLING, Inst Life Sci, Singapore, Singapore..
    Checa, Antonio
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden..
    Cinel, Michelle A.
    Baker Heart & Diabet Inst, Melbourne, Vic, Australia..
    Colas, Romain A.
    Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Cremers, Serge
    Columbia Univ, Med Ctr, Irving Inst Clin & Translat Res, Biomarker Core Lab, New York, NY USA..
    Dennis, Edward A.
    Univ Calif San Diego, Sch Med, Dept Chem & Biochem, La Jolla, CA 92093 USA.;Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA..
    Evans, James E.
    Roskamp Inst, Sarasota, FL USA..
    Fauland, Alexander
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden..
    Fiehn, Oliver
    Univ Calif Davis, Genome Ctr, Natl Inst Hlth West Coast Metabol Ctr, Davis, CA 95616 USA.;King Abdulaziz Univ, Biochem Dept, Jeddah, Saudi Arabia..
    Gardner, Michael S.
    Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Div Lab Sci, Atlanta, GA USA..
    Garrett, Timothy J.
    Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA..
    Gotlinger, Katherine H.
    New York Med Coll, Sch Med, Dept Pharmacol, Valhalla, NY 10595 USA..
    Han, Jun
    Univ Victoria, Genome British Columbia Prote Ctr, Victoria, BC, Canada..
    Huang, Yingying
    Thermo Fisher Sci, San Jose, CA USA..
    Neo, Aveline Huipeng
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore.;Singapore Lipidomic Incubator SLING, Inst Life Sci, Singapore, Singapore..
    Hyotylainen, Tuulia
    Orebro Univ, Dept Chem, Orebro, Sweden..
    Izumi, Yoshihiro
    Kyushu Univ, Med Inst Bioregulat, Res Ctr Trans Med, Div Metabol,Higashi Ku, Fukuoka, Japan..
    Jiang, Hongfeng
    Columbia Univ, Med Ctr, Irving Inst Clin & Translat Res, Biomarker Core Lab, New York, NY USA..
    Jiang, Houli
    New York Med Coll, Sch Med, Dept Pharmacol, Valhalla, NY 10595 USA..
    Jiang, Jiang
    Univ Calif San Diego, Sch Med, Dept Chem & Biochem, La Jolla, CA 92093 USA.;Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA..
    Kachman, Maureen
    Univ Michigan, BRCF, Metabol Core, Ann Arbor, MI 48109 USA..
    Kiyonami, Reiko
    Thermo Fisher Sci, San Jose, CA USA..
    Klavins, Kristaps
    Biocrates Life Sci AG, Innsbruck, Austria..
    Klose, Christian
    Lipotype GmbH, Dresden, Germany..
    Kofeler, Harald C.
    Med Univ Graz, Core Facil Mass Spectrometry, Graz, Austria..
    Kolmert, Johan
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden..
    Koal, Therese
    Biocrates Life Sci AG, Innsbruck, Austria..
    Koster, Grielof
    Univ Southampton, Southampton Gen Hosp, Acad Unit Clin & Expt Sci, Fac Med, Southampton, Hants, England..
    Kuklenyik, Zsuzsanna
    Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Div Lab Sci, Atlanta, GA USA..
    Kurland, Irwin J.
    Albert Einstein Coll Med, Diabet Res Ctr, Stable Isotope & Metabol Core Facil, Bronx, NY 10467 USA..
    Leadley, Michael
    Hosp Sick Children, Res Inst, Analyt Facil Bioact Mol, Toronto, ON, Canada..
    Lin, Karen
    Univ Victoria, Genome British Columbia Prote Ctr, Victoria, BC, Canada..
    Maddipati, Krishna Rao
    Wayne State Univ, Lipid Core Facil, Detroit, MI USA.;Wayne State Univ, Dept Pathol, Detroit, MI USA..
    McDougall, Danielle
    Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA..
    Meikle, Peter J.
    Baker Heart & Diabet Inst, Melbourne, Vic, Australia..
    Mellett, Natalie A.
    Baker Heart & Diabet Inst, Melbourne, Vic, Australia..
    Monnin, Cian
    Concordia Univ, Dept Chem & Biochem, Montreal, PQ, Canada..
    Moseley, M. Arthur
    Duke Univ, Sch Med, Levine Sci Res Ctr, Prote & Metabol Shared Resource, Durham, NC USA..
    Nandakumar, Renu
    Columbia Univ, Med Ctr, Irving Inst Clin & Translat Res, Biomarker Core Lab, New York, NY USA.;Lipotype GmbH, Dresden, Germany..
    Oresic, Matej
    Univ Turku, Turku Ctr Biotechnol, Turku, Finland.;Abo Akad Univ, Turku, Finland..
    Patterson, Rainey
    Peake, David
    Pierce, Jason S.
    Post, Martin
    Hosp Sick Children, Res Inst, Analyt Facil Bioact Mol, Toronto, ON, Canada..
    Postle, Anthony D.
    Pugh, Rebecca
    NIST, Chem Sci Div, Environm Specimen Bank Grp, Hollings Marine Lab, Charleston, SC USA..
    Qiu, Yunping
    Albert Einstein Coll Med, Diabet Res Ctr, Stable Isotope & Metabol Core Facil, Bronx, NY 10467 USA..
    Quehenberger, Oswald
    Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.;Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA..
    Ramrup, Parsram
    Rees, Jon
    Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Div Lab Sci, Atlanta, GA USA..
    Rembiesa, Barbara
    Med Univ South Carolina, Dept Biochem & Mol Biol, Charleston, SC USA..
    Reynaud, Denis
    Hosp Sick Children, Res Inst, Analyt Facil Bioact Mol, Toronto, ON, Canada..
    Roth, Mary R.
    Kansas State Univ, Kansas Lipid Res Ctr, Div Biol, Manhattan, KS 66506 USA..
    Sales, Susanne
    Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany..
    Schuhmann, Kai
    Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany..
    Schwartzman, Michal Laniado
    New York Med Coll, Sch Med, Dept Pharmacol, Valhalla, NY 10595 USA..
    Serhan, Charles N.
    Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Shevchenko, Andrej
    Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany..
    Somerville, Stephen E.
    Med Univ South Carolina, Hollings Marine Lab, Charleston, SC USA..
    John-Williams, Lisa St.
    Duke Univ, Sch Med, Levine Sci Res Ctr, Prote & Metabol Shared Resource, Durham, NC USA..
    Surma, Michal A.
    Univ Michigan, BRCF, Metabol Core, Ann Arbor, MI 48109 USA..
    Takeda, Hiroaki
    Kyushu Univ, Med Inst Bioregulat, Res Ctr Trans Med, Div Metabol,Higashi Ku, Fukuoka, Japan..
    Thakare, Rhishikesh
    Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE USA..
    Thompson, J. Will
    Duke Univ, Sch Med, Levine Sci Res Ctr, Prote & Metabol Shared Resource, Durham, NC USA..
    Torta, Federico
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore.;Singapore Lipidomic Incubator SLING, Inst Life Sci, Singapore, Singapore..
    Triebl, Alexander
    Med Univ Graz, Core Facil Mass Spectrometry, Graz, Austria..
    Troetzmueller, Martin
    Med Univ Graz, Core Facil Mass Spectrometry, Graz, Austria..
    Ubhayasekera, S. J. Kumari
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Vuckovic, Dajana
    Weir, Jacquelyn M.
    Baker Heart & Diabet Inst, Melbourne, Vic, Australia..
    Welti, Ruth
    Kansas State Univ, Kansas Lipid Res Ctr, Div Biol, Manhattan, KS 66506 USA..
    Wenk, Markus R.
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore.;Singapore Lipidomic Incubator SLING, Inst Life Sci, Singapore, Singapore..
    Wheelock, Craig E.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden..
    Yao, Libin
    Kansas State Univ, Kansas Lipid Res Ctr, Div Biol, Manhattan, KS 66506 USA..
    Yuan, Min
    Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA..
    Zhao, Xueqing Heather
    Albert Einstein Coll Med, Diabet Res Ctr, Stable Isotope & Metabol Core Facil, Bronx, NY 10467 USA..
    Zhou, Senlin
    Wayne State Univ, Lipid Core Facil, Detroit, MI USA.;Wayne State Univ, Dept Pathol, Detroit, MI USA..
    Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma2017Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 58, nr 12, s. 2275-2288Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

  • 162. Bozaykut, Perinur
    et al.
    Sozen, Erdi
    Kaga, Elif
    Ece, Asli
    Ozaltin, Esra
    Ek, Bo
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ozer, Nesrin Kartal
    Grune, Tilman
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Karademir, Betul
    The role of heat stress on the age related protein carbonylation2013Inngår i: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 89, s. 238-254Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Since the proteins are involved in many physiological processes in the organisms, modifications of proteins have important outcomes. Protein modifications are classified in several ways and oxidative stress related ones take a wide place. Aging is characterized by the accumulation of oxidized proteins and decreased degradation of these proteins. On the other hand protein turnover is an important regulatory mechanism for the control of protein homeostasis. Heat shock proteins are a highly conserved family of proteins in the various cells and organisms whose expressions are highly inducible during stress conditions. These proteins participate in protein assembly, trafficking, degradation and therefore play important role in protein turnover. Although the entire functions of each heat shock protein are still not completely investigated, these proteins have been implicated in the processes of protection and repair of stress-induced protein damage. This study has focused on the heat stress related carbonylated proteins, as a marker of oxidative protein modification, in young and senescent fibroblasts. The results are discussed with reference to potential involvement of induced heat shock proteins. This article is part of a Special Issue entitled: Protein Modifications. Biological significance Age-related protein modifications, especially protein carbonylation take a wide place in the literature. In this direction, to highlight the role of heat shock proteins in the oxidative modifications may bring a new aspect to the literature. On the other hand, identified carbonylated proteins in this study confirm the importance of folding process in the mitochondria which will be further analyzed in detail.

  • 163.
    Brishammar, Sture
    et al.
    MASE Laboratory, Uppsala, Sweden.
    Hanrieder, Jörg
    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.
    TMV-particle borne enhancer of a tobacco RNA-replicase2012Inngår i: World Journal of Science and Technology, ISSN 2231-2587, Vol. 2, nr 7, s. 4-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    According to separation studies it has been evident that a tobacco RNA-replicase after TMV-infection consists of two parts. The larger part is host-directed and will be combined with a virus borne small protein which considerably enhances the RNA-replicase activity and is therefore named replicase enhancer, Ree. This compound was found at HPLC-separations of TMV-coat proteins, and was detected using polymerase assay with a radioactive nucleotide involved. Molecular weight has been determined by mass spectrometry: with FT ICR MS to get the size – 6 023.3 - and with MALDI TOF MS to obtain a sequence of the 54 amino acids involved. Presumably Ree is fixed to the TMV-RNA at infection. The enzyme seems to produce minus-strands of the virus RNA.

  • 164.
    Bunrit, Anon
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Olsson, Sandra K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Srifa, Pemikar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Huang, Genping
    Orthaber, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Sjöberg, Per J. R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Biswas, Srijit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Himo, Fahmi
    Samec, Joseph S. M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Bronsted Acid-Catalyzed Intramolecular Nucleophilic Substitution of the Hydroxyl Group in Stereogenic Alcohols with Chirality Transfer2015Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 137, nr 14, s. 4646-4649Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The hydroxyl group of enantioenriched benzyl, propargyl, allyl, and alkyl alcohols has been intramolecularly displaced by uncharged O-, N-, and S-centered nucleophiles to yield enantioenriched tetrahydrofuran, pyrrolidine, and tetrahydrothiophene derivatives with phosphinic acid catalysis. The five-membered heterocyclic products are generated in good to excellent yields, with high degree of chirality transfer, and water as the only side-product. Racemization experiments show that phosphinic acid does not promote S(N)1 reactivity. Density functional theory calculations corroborate a reaction pathway where the phosphinic acid operates as a bifunctional catalyst in the intramolecular substitution reaction. In this mechanism, the acidic proton of the phosphinic acid protonates the hydroxyl group, enhancing the leaving group ability. Simultaneously, the oxo group of phosphinic acid operates as a base abstracting the nucleophilic proton and thus enhancing the nucleophilicity. This reaction will open up new atom efficient techniques that enable alcohols to be used as nucleofuges in substitution reactions in the future.

  • 165.
    Bunrit, Anon
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Srifa, Pemikar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Olsson, Sandra K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Huang, Genping
    Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden.;Tianjin Univ, Sch Sci, Dept Chem, Tianjin 300072, Peoples R China..
    Biswas, Srijit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Ctr Biomed Res, Lucknow 226014, Uttar Pradesh, India..
    Himo, Fahmi
    Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Samec, Joseph S. M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Nucleophilic Substitution of the Hydroxyl Group in Stereogenic Alcohols with Chirality Transfer2016Inngår i: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 27, nr 2, s. 173-176Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A brief overview of the development of direct substitution of the hydroxyl (OH) group of alcohols in our research group is presented. By applying a BrOnsted acid, an intramolecular substitution of the OH group in stereogenic alcohols with chirality transfer was achieved. Noteworthy, the intramolecular substitution has a wide scope in respect to both the nucleophile and also the nucleofuge. A mechanistic study by both experiments and DFT calculations revealed a unique reaction pathway in which the BrOnsted acid operates in a bifunctional manner to promote an S(N)2-type reaction mechanism.

  • 166.
    Bunrit, Anon
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    Sawadjoon, Supaporn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Tsupova, Svetlana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Sjöberg, Per J. R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Samec, Joseph S. M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Stockholm Univ, Dept Organ Chem, S-10691 Stockholm, Sweden..
    A General Route to beta-Substituted Pyrroles by Transition-Metal Catalysis2016Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 81, nr 4, s. 1450-1460Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An atom-efficient route to pyrroles substituted in the beta-position has been achieved in four high yielding steps by a combination of Pd, Ru, and Fe catalysis with only water and ethene as side-products. The reaction is general and gives pyrroles substituted in the beta-position with linear and branched alkyl, benzyl, or aryl groups in overall good yields. The synthetic route includes a Pd-catalyzed monoallylation step of amines with substituted allylic alcohols that proceeds to yield the monoallylated products in moderate to excellent yields. In a second step, unsymmetrical diallylated aromatic amines are generated from the reaction of a second allylic alcohol with high selectivity in moderate to good yields by control of the reaction temperature. Ru-catalyzed ring-closing metathesis performed on the diallylated aromatic amines yields the pyrrolines substituted in the beta-position in excellent yields. By addition of ferric chloride to the reaction mixture, a selective aromatization to yield the corresponding pyrroles substituted in the beta-position was achieved. A reaction mechanism involving a palladium hydride, generated from insertion of palladium to O-H of an allyl alcohol, that is responsible for the C-O bond cleavage to generate the pi-allyl intermediate is proposed.

  • 167.
    Bunrit, Anon
    et al.
    Stockholm Univ, Organ Chem, Stockholm, Sweden..
    Watile, Rahul
    Stockholm Univ, Organ Chem, Stockholm, Sweden..
    Dahlstrand, Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Olsson, Sandra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Srifa, Pemikar
    Stockholm Univ, Organ Chem, Stockholm, Sweden..
    Huang, Genping
    Stockholm Univ, Organ Chem, Stockholm, Sweden..
    Biswas, Srijit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Himo, Fahmi
    Stockholm Univ, Organ Chem, Stockholm, Sweden..
    Samec, Joseph
    Stockholm Univ, Organ Chem, Stockholm, Sweden..
    H3PO2-catalyzed intramolecular stereospecific nucleophilic substitution of the hydroxyl group in stereogenic alcohols2017Inngår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 254Artikkel i tidsskrift (Annet vitenskapelig)
  • 168.
    Burke, Jason R.
    et al.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;Calif State Univ San Bernardino, San Bernardino, CA 92407 USA.
    La Clair, James J.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
    Philippe, Ryan N.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;Manus Biosynth, Cambridge, MA USA.
    Pabis, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturbiologi.
    Corbella, Marina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Jez, Joseph M.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;Washington Univ, Dept Biol, Howard Hughes Med Inst, Campus Box 1137, St Louis, MO 63130 USA.
    Cortina, George A.
    Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22903 USA.
    Kaltenbach, Miriam
    Weizmann Inst Sci, Dept Biomol Sci, IL-76100 Rehovot, Israel.
    Bowman, Marianne E.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
    Louie, Gordon V.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
    Woods, Katherine B.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
    Nelson, Andrew T.
    Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.
    Tawfik, Dan S.
    Weizmann Inst Sci, Dept Biomol Sci, IL-76100 Rehovot, Israel.
    Kamerlin, Shina C. Lynn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Noel, Joseph P.
    Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, Howard Hughes Med Inst, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
    Bifunctional Substrate Activation via an Arginine Residue Drives Catalysis in Chalcone Isomerases2019Inngår i: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 9, nr 9, s. 8388-8396Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chalcone isomerases are plant enzymes that perform enantioselective oxa-Michael cyclizations of 2'-hydroxychalcones into flavanones. An X-ray crystal structure of an enzyme-product complex combined with molecular dynamics simulations reveal an enzyme mechanism wherein the guanidinium ion of a conserved arginine positions the nucleophilic phenoxide and activates the electrophilic enone for cyclization through Bronsted and Lewis acid interactions. The reaction terminates by asymmetric protonation of the carbanion intermediate syn to the guanidinium. Interestingly, bifunctional guanidine- and urea-based chemical reagents, increasingly used for asymmetric organocatalytic applications, share mechanistic similarities with this natural system. Comparative protein crystal structures and molecular dynamics simulations further demonstrate how two active site water molecules coordinate a hydrogen bond network that enables expanded substrate reactivity for 6'-deoxychalcones in more recently evolved type-2 chalcone isomerases.

  • 169.
    Bykov, I.
    et al.
    Royal Inst Technol KTH, Div Fus Plasma Phys, Stockholm, Sweden..
    Bergsåker, H.
    Royal Inst Technol KTH, Div Fus Plasma Phys, Stockholm, Sweden..
    Possnert, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, För teknisk-naturvetenskapliga fakulteten gemensamma enheter, Tandemlaboratoriet.
    Zhou, Y.
    Royal Inst Technol KTH, Div Fus Plasma Phys, Stockholm, Sweden..
    Heinola, K.
    Univ Helsinki, Dept Phys, POB 64, Helsinki 00560, Finland..
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Conroy, Sean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Tillämpad kärnfysik.
    Likonen, J.
    VTT, POB 1000, Espoo 02044, Finland..
    Petersson, P.
    Royal Inst Technol KTH, Div Fus Plasma Phys, Stockholm, Sweden..
    Widdowson, A.
    EUROfus Consortium, JET, Culham Sci Ctr, Abingdon OX14 3DB, Oxon, England..
    Studies of Be migration in the JET tokamak using AMS with Be-10 marker2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The JET tokamak is operated with beryllium limiter tiles in the main chamber and tungsten coated carbon fiber composite tiles and solid W tiles in the divertor. One important issue is how wall materials are migrating during plasma operation. To study beryllium redistribution in the main chamber and in the divertor, a Be-10 enriched limiter tile was installed prior to plasma operations in 2011-2012. Methods to take surface samples have been developed, an abrasive method for bulk Be tiles in the main chamber, which permits reuse of the tiles, and leaching with hot HCl to remove all Be deposited at W coated surfaces in the divertor. Quantitative analysis of the total amount of Be in cm(2) sized samples was made with inductively coupled plasma atomic emission spectroscopy (ICP-AES). The Be-10/Be-9 ratio in the samples was measured with accelerator mass spectrometry (AMS). The experimental setup and methods are described in detail, including sample preparation, measures to eliminate contributions in AMS from the B-10 isobar, possible activation due to plasma generated neutrons and effects of diffusive isotope mixing. For the first time marker concentrations are measured in the divertor deposits. They are in the range 0.4-1.2% of the source concentration, with moderate poloidal variation.

  • 170. Bäckbro, Kristina
    et al.
    Andersson, Hans
    Bonham, Nick M
    Classon, Björn
    Danielson, U Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Hallberg, Anders
    Hultén, Johan
    Karlén, Anders
    Löwgren, Seved
    Nillroth, Ulrika
    Schaal, Wesley
    Unge, Torsten
    Cyclic urea and sulfamide-based inhibitors of HIV-1 protease: Changes in binding mode upon modifications in the P1/P1 side chain1998Inngår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 37, s. A56-A56Artikkel i tidsskrift (Fagfellevurdert)
  • 171.
    Cadu, Alban
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Iridium Catalysed Asymmetric Hydrogenation of Pyridines2013Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis presents the hydrogenation of substituted pyridines using N,P-ligated iridium catalystsin homogeneous media. These iridium catalysts were developed within this research group in thepast decade. This method of hydrogenation is highly stereoselective, and in several cases good to excellent ees were obtained.The hydrogenation of substituted pyridines was studied: by screening for the catalyst giving thehighest conversion and ee, by optimising the reaction conditions and by attempting to improve existingcatalysts. New substrates were synthesised for this process, in particular alkyl substituted Nprotectedpyridines. Their reduction provided chiral piperidines, which could be used as chiralbuilding blocks once deprotected.

    Delarbeid
    1. Iridium-Catalyzed Asymmetric Hydrogenation of Substituted Pyridines
    Åpne denne publikasjonen i ny fane eller vindu >>Iridium-Catalyzed Asymmetric Hydrogenation of Substituted Pyridines
    2013 (engelsk)Inngår i: Asian Journal of Organic Chemistry, ISSN 2193-5807, Vol. 2, nr 12, s. 1061-1065Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Asymmetric hydrogenation of ortho-substituted pyridines catalyzed by N,P-ligated iridium is demonstrated. To facilitate this reaction, the aromaticity of the pyridines was weakened by forming N-iminopyridium ylides. The reactions give very high conversions, and after a single recrystallization, excellent ee of up to 98 % was obtained. This method lends itself to the synthesis of chiral piperidine building blocks.

    Emneord
    hydrogenation, iridium, N-iminopyridium ylides, pyridines, selective catalysis
    HSV kategori
    Forskningsprogram
    Organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-212412 (URN)10.1002/ajoc.201300160 (DOI)000328218000008 ()
    Tilgjengelig fra: 2013-12-10 Laget: 2013-12-10 Sist oppdatert: 2017-01-25bibliografisk kontrollert
  • 172.
    Cadu, Alban
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Noble Metal Catalysed Reductions and Rearrangements2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The focus of this thesis has been organometallic catalysis applied to compounds containing heteroatoms which are usually poisonous to metal catalysts, by channelling their innate reactivity advantageously. The studies described in this thesis concentrate, in the first part, on iridium catalysed asymmetric hydrogenation (papers I and II) and in the second part, on gold catalysed internal rearrangements (papers III and IV). In each case, two classes of compounds are studied: pyridinium salts or sulphurous compounds. The asymmetric hydrogenation of pyridinium compounds was performed with 2% loading of N,P-ligated Ir catalyst with I2 additive (paper I) to achieve moderate to good enantiomeric excess (up to 98%). In paper II, olefinic sulphones were hydrogenated with an efficient 0.5% catalytic loading. In most cases full conversion was obtained and with good to excellent ees (up to 99%). The products of these reductions are chiral compounds, which could constitute further chemical building blocks. Palladium and gold were used sequentially in paper III, in order to perform a “Click” thiol-yne reaction followed by a semi-Pinacol rearrangement, leading to isolated yields of up to 98%. In paper IV The gold catalysed rearrangement of alkyl-pyridinium diynes was conducted, with a number of substrates providing >90% NMR yield. A highly selective hydrogenation was performed with a heterogeneous palladium catalyst to yield single diastereomer products. This methodology consists of up to three steps, with two catalysts in one pot.

    Delarbeid
    1. Iridium-Catalyzed Asymmetric Hydrogenation of Substituted Pyridines
    Åpne denne publikasjonen i ny fane eller vindu >>Iridium-Catalyzed Asymmetric Hydrogenation of Substituted Pyridines
    2013 (engelsk)Inngår i: Asian Journal of Organic Chemistry, ISSN 2193-5807, Vol. 2, nr 12, s. 1061-1065Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Asymmetric hydrogenation of ortho-substituted pyridines catalyzed by N,P-ligated iridium is demonstrated. To facilitate this reaction, the aromaticity of the pyridines was weakened by forming N-iminopyridium ylides. The reactions give very high conversions, and after a single recrystallization, excellent ee of up to 98 % was obtained. This method lends itself to the synthesis of chiral piperidine building blocks.

    Emneord
    hydrogenation, iridium, N-iminopyridium ylides, pyridines, selective catalysis
    HSV kategori
    Forskningsprogram
    Organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-212412 (URN)10.1002/ajoc.201300160 (DOI)000328218000008 ()
    Tilgjengelig fra: 2013-12-10 Laget: 2013-12-10 Sist oppdatert: 2017-01-25bibliografisk kontrollert
    2. An Enantioselective Approach to the Preparation of Chiral Sulfones by Ir-Catalyzed Asymmetric Hydrogenation
    Åpne denne publikasjonen i ny fane eller vindu >>An Enantioselective Approach to the Preparation of Chiral Sulfones by Ir-Catalyzed Asymmetric Hydrogenation
    Vise andre…
    2014 (engelsk)Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 136, nr 47, s. 16557-16562Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Several chiral sulfonyl compounds were prepared using the iridium catalyzed asymmetric hydrogenation reaction. Vinylic, allylic and homoallylic sulfone substitutions were investigated, and high enantioselectivity is maintained regardless of the location of the olefin with respect to the sulfone. Impressive stereoselectivity was obtained for dialkyl substitutions, which typically are challenging substrates in the hydrogenation. As expected, the more bulky Z-substrates were hydrogenated slower than the corresponding E isomers, and in slightly lower enantioselectivity.

    sted, utgiver, år, opplag, sider
    American Chemical Society (ACS), 2014
    HSV kategori
    Forskningsprogram
    Organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-236862 (URN)10.1021/ja5079877 (DOI)000345720500016 ()25300238 (PubMedID)
    Tilgjengelig fra: 2014-11-24 Laget: 2014-11-24 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    3. One-Pot Synthesis of Keto Thioethers by Palladium/Gold-Catalyzed Click and Pinacol Reactions
    Åpne denne publikasjonen i ny fane eller vindu >>One-Pot Synthesis of Keto Thioethers by Palladium/Gold-Catalyzed Click and Pinacol Reactions
    Vise andre…
    2014 (engelsk)Inngår i: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 16, nr 21, s. 5556-5559Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    An atom-efficient synthesis of keto thioethers was devised via tandem gold/palladium catalysis. The reaction proceeds through a regioselective thiol attack at the β-position of the alcohol, followed by an alkyl, aryl, or benzyl 1,2-shift. Both acyclic and cyclic systems were studied, in the latter case leading to the ring expansion of cyclic substrates.

    sted, utgiver, år, opplag, sider
    American Chemical Society (ACS), 2014
    Emneord
    Gold, Palladium, thioether, catalysis, synthesis
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-236857 (URN)10.1021/ol502553p (DOI)000344635200013 ()25325145 (PubMedID)
    Tilgjengelig fra: 2014-11-24 Laget: 2014-11-24 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    4. Dual Gold (I) Catalysed Cyclisation of Dialkynyl Pyridinium salts
    Åpne denne publikasjonen i ny fane eller vindu >>Dual Gold (I) Catalysed Cyclisation of Dialkynyl Pyridinium salts
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Novel dialkynyl pyridines were synthesised and protected as alkyl salts for dual gold (I) catalysed cycloisomerisation. Different alkyl groups and counter ions were screened for the salts, with benzyl and PF6- providing the best results. The cyclisation led to NMR yields of >95% being obtained for a number of substrates. Step-wise hydrogenation of products could be carried out in one-pot by Pd/C, with selective reduction of the double bonds, followed by deprotection of the Bn group.

    Emneord
    chemistry
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-272369 (URN)
    Tilgjengelig fra: 2016-01-13 Laget: 2016-01-13 Sist oppdatert: 2016-02-12bibliografisk kontrollert
  • 173.
    Cadu, Alban
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Andersson, Pher G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Development of iridium-catalyzed asymmetric hydrogenation: New catalysts, new substrate scope2012Inngår i: Journal of Organometallic Chemistry, ISSN 0022-328X, E-ISSN 1872-8561, Vol. 714, s. 3-11Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    A review. The asym. hydrogenation of olefins is a tremendously powerful tool used to synthesize chiral mols. The field was pioneered using rhodium- and ruthenium- based catalysts; however, catalysts based on both of these metals suffer from limitations, such as the need for directing substituents near or even adjacent to the olefin. Iridium-based catalysts do not suffer from this flaw and can thus hydrogenate a wide variety of olefins, including some tetra substituted ones. It is also possible for iridium-based catalysts to hydrogenate hetero-π bonds such as those found in heteroarom. rings. This review summarizes the contributions made to this field by the authors in the past few years. [on SciFinder(R)]

  • 174.
    Cadu, Alban
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Andersson, Pher G
    Iridium catalysis: Application of asymmetric reductive hydrogenation2013Inngår i: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 42, nr 40, s. 14345-14356Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Iridium, despite being one of the least abundant transition metals, has found several uses. N,P-ligated iridium catalysts are used to perform many highly selective reactions. These methodologies have been developed extensively over the past 15 years. More recently, the application of iridium N,P catalysts in asymmetric hydrogenation has been a focus of research to find novel applications and to expand on their current synthetic utility. The aim of this perspective is to highlight the advances made by the Andersson group.

  • 175.
    Cadu, Alban
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Upadhyay, Puspesh K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Andersson, Pher G.
    Stockholm University.
    Iridium-Catalyzed Asymmetric Hydrogenation of Substituted Pyridines2013Inngår i: Asian Journal of Organic Chemistry, ISSN 2193-5807, Vol. 2, nr 12, s. 1061-1065Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Asymmetric hydrogenation of ortho-substituted pyridines catalyzed by N,P-ligated iridium is demonstrated. To facilitate this reaction, the aromaticity of the pyridines was weakened by forming N-iminopyridium ylides. The reactions give very high conversions, and after a single recrystallization, excellent ee of up to 98 % was obtained. This method lends itself to the synthesis of chiral piperidine building blocks.

  • 176.
    Cadu, Alban
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Watile, Rahul
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Biswas, Srijit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Orthaber, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström.
    Sjöberg, Per J
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Samec, Joseph
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    One-Pot Synthesis of Keto Thioethers by Palladium/Gold-Catalyzed Click and Pinacol Reactions2014Inngår i: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 16, nr 21, s. 5556-5559Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An atom-efficient synthesis of keto thioethers was devised via tandem gold/palladium catalysis. The reaction proceeds through a regioselective thiol attack at the β-position of the alcohol, followed by an alkyl, aryl, or benzyl 1,2-shift. Both acyclic and cyclic systems were studied, in the latter case leading to the ring expansion of cyclic substrates.

  • 177.
    Cagatay, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Production of human β-alanine synthase for crystallographic studies2014Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 178.
    Calixto, Ana R.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Moreira, Catia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Pabis, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Kötting, Carsten
    Ruhr Univ Bochum, Dept Biophys, D-44801 Bochum, Germany.
    Gerwert, Klaus
    Ruhr Univ Bochum, Dept Biophys, D-44801 Bochum, Germany.
    Rudack, Till
    Ruhr Univ Bochum, Dept Biophys, D-44801 Bochum, Germany.
    Kamerlin, Shina C. Lynn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    GTP Hydrolysis Without an Active Site Base: A Unifying Mechanism for Ras and Related GTPases2019Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 141, nr 27, s. 10684-10701Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    GTP hydrolysis is a biologically crucial reaction, being involved in regulating almost all cellular processes. As a result, the enzymes that catalyze this reaction are among the most important drug targets. Despite their vital importance and decades of substantial research effort, the fundamental mechanism of enzyme-catalyzed GTP hydrolysis by GTPases remains highly controversial. Specifically, how do these regulatory proteins hydrolyze GTP without an obvious general base in the active site to activate the water molecule for nucleophilic attack? To answer this question, we perform empirical valence bond simulations of GTPase-catalyzed GTP hydrolysis, comparing solvent- and substrate-assisted pathways in three distinct GTPases, Ras, Rab, and the G(alpha i), subunit of a heterotrimeric G-protein, both in the presence and in the absence of the corresponding GTPase activating proteins. Our results demonstrate that a general base is not needed in the active site, as the preferred mechanism for GTP hydrolysis is a conserved solvent-assisted pathway. This pathway involves the rate-limiting nucleophilic attack of a water molecule, leading to a short-lived intermediate that tautomerizes to form H2PO4- and GDP as the final products. Our fundamental biochemical insight into the enzymatic regulation of GTP hydrolysis not only resolves a decades-old mechanistic controversy but also has high relevance for drug discovery efforts. That is, revisiting the role of oncogenic mutants with respect to our mechanistic findings would pave the way for a new starting point to discover drugs for (so far) "undruggable" GTPases like Ras.

  • 179.
    Calixto, Ana Rita
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi. Univ Porto, Dept Quim & Bioquim, UCIBIO REQUIMTE, Fac Ciencias, Rua Campo Alegre S-N, P-4169007 Porto, Portugal.
    Ramos, Maria Joao
    Univ Porto, Dept Quim & Bioquim, UCIBIO REQUIMTE, Fac Ciencias, Rua Campo Alegre S-N, P-4169007 Porto, Portugal.
    Fernandes, Pedro Alexandrino
    Univ Porto, Dept Quim & Bioquim, UCIBIO REQUIMTE, Fac Ciencias, Rua Campo Alegre S-N, P-4169007 Porto, Portugal.
    Conformational diversity induces nanosecond-timescale chemical disorder in the HIV-1 protease reaction pathway2019Inngår i: Chemical Science, ISSN 2041-6520, E-ISSN 2041-6539, Vol. 10, nr 30, s. 7212-7221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The role of conformational diversity in enzyme catalysis has been a matter of analysis in recent studies. Pre-organization of the active site has been pointed out as the major source for enzymes' catalytic power. Following this line of thought, it is becoming clear that specific, instantaneous, non-rare enzyme conformations that make the active site perfectly pre-organized for the reaction lead to the lowest activation barriers that mostly contribute to the macroscopically observed reaction rate. The present work is focused on exploring the relationship between structure and catalysis in HIV-1 protease (PR) with an adiabatic mapping method, starting from different initial structures, collected from a classical MD simulation. The first, rate-limiting step of the HIV-1 PR catalytic mechanism was studied with the ONIOM QM/MM methodology (B3LYP/6-31G(d):ff99SB), with activation and reaction energies calculated at the M06-2X/6-311++G(2d,2p):ff99SB level of theory, in 19 different enzyme:substrate conformations. The results showed that the instantaneous enzyme conformations have two independent consequences on the enzyme's chemistry: they influence the barrier height, something also observed in the past in other enzymes, and they also influence the specific reaction pathway, which is something unusual and unexpected, challenging the "one enzyme-one substrate-one reaction mechanism" paradigm. Two different reaction mechanisms, with similar reactant probabilities and barrier heights, lead to the same gem-diol intermediate. Subtle nanosecond-timescale rearrangements in the active site hydrogen bonding network were shown to determine which reaction the enzyme follows. We named this phenomenon chemical disorder. The results make us realize the unexpected mechanistic consequences of conformational diversity in enzymatic reactivity.

  • 180.
    Cardoso-Palacios, Carlos
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Lanekoff, Ingela
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Direct Analysis of Pharmaceutical Drugs Using Nano-DESI MS2016Inngår i: Journal of Analytical Methods in Chemistry, ISSN 2090-8865, E-ISSN 2090-8873, artikkel-id 3591908Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Counterfeit pharmaceutical drugs imply an increasing threat to the global public health. It is necessary to have systems to control the products that reach the market and to detect falsified medicines. In this work, molecules in several pharmaceutical tablets were directly analyzed using nanospray desorption electrospray ionization mass spectrometry (nano-DESI MS). Nano-DESI is an ambient surface sampling technique which enables sampling of molecules directly from the surface of the tablets without any sample pretreatment. Both the active pharmaceutical ingredients (APIs) and some excipients were detected in all analyzed tablets. Principal component analysis was used to analyze mass spectral features from different tablets showing strong clustering between tablets with different APIs. The obtained results suggest nano-DESI MS as future tool for forensic analysis to discern APIs present in unknown tablet samples.

  • 181.
    Carlsson, Anna-Carin C
    et al.
    Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
    Grafenstein, Jurgen
    Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
    Budnjo, Adnan
    Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
    Laurila, Jesse L
    Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Karim, Alavi
    Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
    Kleinmaier, Roland
    Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
    Brath, Ulrika
    Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
    Erdelyi, Mate
    Department of Chemistry and Molecular Biology, University of Gothenburg and The Swedish NMR Centre, Gothenburg, Sweden.
    Symmetric halogen bonding is preferred in solution2012Inngår i: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, nr 12, s. 5706-5715Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Halogen bonding is a recently rediscovered secondary interaction that shows potential to become a complementary molecular tool to hydrogen bonding in rational drug design and in material sciences. Whereas hydrogen bond symmetry has been the subject of systematic studies for decades, the understanding of the analogous three-center halogen bonds is yet in its infancy. The isotopic perturbation of equilibrium (IPE) technique with 13C NMR detection was applied to regioselectively-deuterated pyridine complexes to investigate the symmetry of [N–I–N]+ and [N–Br–N]+ halogen bonding in solution. Preference for a symmetric arrangement was observed for both a freely adjustable and for a conformationally restricted [N–X–N]+ model system, as also confirmed by computation on the DFT level. A closely attached counter ion is shown to be compatible with the preferred symmetric arrangement. The experimental observations and computational predictions reveal a high energetic gain upon formation of symmetric, three-center four-electron halogen bonding. Whereas hydrogen bonds are generally asymmetric in solution and symmetric in the crystalline state, the analogous bromine and iodine centered halogen bonds prefer symmetric arrangement in solution.

  • 182.
    Carlsson, Anna-Carin C.
    et al.
    Department of Chemistry and the Swedish NMR Centre, University of Gothenburg, Sweden.
    Grafenstein, Jurgen
    Department of Chemistry and the Swedish NMR Centre, University of Gothenburg, Sweden.
    Laurila, Jesse L.
    Department of Chemistry and the Swedish NMR Centre, University of Gothenburg, Sweden.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Erdelyi, Mate
    Department of Chemistry and the Swedish NMR Centre, University of Gothenburg, Sweden.
    Symmetry of [N-X-N]+ halogen bonds in solution2012Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 48, nr 10, s. 1458-1460Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The first investigation of halogen bond symmetry is presented. In contrast to related hydrogen bonds, the iodous halogen bond is symmetric in solution and in the crystal. The bromous analogue is symmetric in solution, but shows asymmetry in the solid state. NMR results are in agreement with DFT predictions.

  • 183.
    Carlsson, Jörgen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Ghaneolhosseini, H
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Johnsson, M
    Sjöberg, S
    Stabilised liposomes with double targeting intendent for use in BNCT2001Inngår i: Frontiers in Neutron Capture Therapy: Volume 1 / [ed] M Frederick Hawthorne, Kenneth Shelly, Richard J Wiersema, 2001, s. 184-Konferansepaper (Annet vitenskapelig)
  • 184.
    Caron, Giulia
    et al.
    Univ Torino, Mol Biotechnol & Hlth Sci Dept, Via Quarello 15, I-10135 Turin, Italy.
    Kihlberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Ermondi, Giuseppe
    Univ Torino, Mol Biotechnol & Hlth Sci Dept, Via Quarello 15, I-10135 Turin, Italy.
    Intramolecular hydrogen bonding: An opportunity for improved design in medicinal chemistry2019Inngår i: Medicinal research reviews (Print), ISSN 0198-6325, E-ISSN 1098-1128, Vol. 39, nr 5, s. 1707-1729Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Recent literature shows that intramolecular hydrogen bond (IMHB) formation can positively impact upon the triad of permeability, solubility, and potency of drugs and candidates. IMHB modulation can be applied to compounds in any chemical space as a means for discovering drug candidates with both acceptable potency and absorption, distribution, metabolism, and excretion-Tox profiles. Integrating IMHB formation in design of drugs is, therefore, an exciting and timely challenge for modern medicinal chemistry. In this review, we first provide some background about IMHBs from the medicinal chemist's point of view and highlight some IMHB-associated misconceptions. Second, we propose a classification of IMHBs for drug discovery purposes, review the most common in silico tactics to include IMHBs in lead optimization and list some experimental physicochemical descriptors, which quantify the propensity of compounds to form IMHBs. By focusing on the compounds size and the number of IMHBs that can potentially be formed, we also outline the major difficulties encountered when designing compounds based on the inclusion of IMHBs. Finally, we discuss recent case studies illustrating the application of IMHB to optimize cell permeability and physicochemical properties of small molecules, cyclic peptides and macrocycles.

  • 185.
    Carter, Sarah-Sophia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Atif, Abdul
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Lanekoff, Ingela
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Tenje, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Mestres, Gemma
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Tailoring the biocompatibility of the elastomer PDMS for on-chip applications2018Konferansepaper (Fagfellevurdert)
  • 186.
    Carter, Sarah-Sophia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Atif, Abdul Raouf M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Lanekoff, Ingela
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Tenje, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Mestres, Gemma
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Improving the biocompatibility of PDMS by improving its curing time and temperature2018Konferansepaper (Annet vitenskapelig)
  • 187. Carter, Stephen F.
    et al.
    Scholl, Michael
    Almkvist, Ove
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Engler, Henry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Nordberg, Agneta
    Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by (11)C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining (11)C-Pittsburgh Compound B and (18)F-FDG2012Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 53, nr 1, s. 37-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Astrocytes colocalize with fibrillar amyloid-beta (A beta) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar A beta. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using (11)C-deuterium-L-deprenyl ((11)C-DED) to measure monoamine oxidase B located in astrocytes. Along with (11)C-DED PET, (11)C-Pittsburgh compound B ((11)C-PIB; fibrillar A beta deposition), (18)F-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: (11)C-DED PET was performed in MCI patients (n = 8; mean age 6 SD, 62.6 +/- 7.5 y; mean Mini Mental State Examination, 27.5 +/- 2.1), AD patients (n = 7; mean age, 65.1 +/- 6.3 y; mean Mini Mental State Examination, 24.4 +/- 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 +/- 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the (11)C-DED data. (11)C-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional (18)F-FDG uptake and (11)C-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional (11)C-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high (11)C-PIB retention. Increased (11)C-DED binding in most cortical and subcortical regions was observed in MCI (11)C-PIB+ patients relative to controls, MCI (11)C-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased (11)C-DED binding throughout the brain of the MCI (11)C-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.

  • 188.
    Cedernaes, Jonathan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schonke, Milena
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Westholm, Jakub Orzechowski
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden.
    Mi, Jia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Binzhou Med Univ, Med & Pharmarcy Res Ctr, Yantai, Peoples R China.
    Chibalin, Alexander
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Voisin, Sarah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Osler, Megan
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Vogel, Heike
    German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Potsdam, Germany.
    Hornaeus, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Dickson, Suzanne L.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Gothenburg, Sweden.
    Lind, Sara
    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. Univ Utah, Dept Pathol, Salt Lake City, UT 84132 USA;Binzhou Med Univ, Precis Med, Yantai, Peoples R China.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Zierath, Juleen R.
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Benedict, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans2018Inngår i: Science Advances, E-ISSN 2375-2548, Vol. 4, nr 8, artikkel-id eaar8590Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.

  • 189. Cele, Zamani E. D.
    et al.
    Sosibo, Sphelele C.
    Andersson, Pher G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Kruger, Hendrik G.
    Maguire, Glenn E. M.
    Govender, Thavendran
    Catalytic asymmetric carbon-carbon bond forming reactions catalyzed by tetrahydroisoquinoline (TIQ) N,N '-dioxide ligands2013Inngår i: Tetrahedron: asymmetry, ISSN 0957-4166, E-ISSN 1362-511X, Vol. 24, nr 4, s. 191-195Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The use of TIQ-N,N'-dioxide ligands in asymmetric C-C bond forming reactions is described. In the Michael addition of cyclohexane-1,3-dione and malonates to beta,gamma-unsaturated alpha-ketoesters, excellent yields (up to 93%) and moderate to good enantioselectivities (70-89% ee) were obtained. The catalytic hetero-ene reaction of 2-methoxypropene with phenylglyoxal gave the ene product in excellent yield (95%) with moderate enantioselectivity (77% ee). The catalyst system performed well at temperatures ranging from 0 to 30 degrees C and relatively low catalyst loading (0.2-5 mol %) with dichloromethane being the preferred solvent for all reactions.

  • 190.
    Chavan, Swapnil
    et al.
    Linnaeus Univ, Linnaeus Univ Ctr Biomat Chem, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, S-39182 Kalmar, Sweden..
    Abdelaziz, Ahmed
    eADMET GmbH, Lichtenbergstr 8, D-85748 Munich, Germany..
    Wiklander, Jesper G.
    Linnaeus Univ, Linnaeus Univ Ctr Biomat Chem, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, S-39182 Kalmar, Sweden..
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Linnaeus Univ, Linnaeus Univ Ctr Biomat Chem, Dept Chem & Biomed Sci, Bioorgan & Biophys Chem Lab, S-39182 Kalmar, Sweden..
    A k-nearest neighbor classification of hERG K+ channel blockers2016Inngår i: Journal of Computer-Aided Molecular Design, ISSN 0920-654X, E-ISSN 1573-4951, Vol. 30, nr 3, s. 229-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A series of 172 molecular structures that block the hERG K+ channel were used to develop a classification model where, initially, eight types of PaDEL fingerprints were used for k-nearest neighbor model development. A consensus model constructed using Extended-CDK, PubChem and Substructure count fingerprint-based models was found to be a robust predictor of hERG activity. This consensus model demonstrated sensitivity and specificity values of 0.78 and 0.61 for the internal dataset compounds and 0.63 and 0.54 for the external (PubChem) dataset compounds, respectively. This model has identified the highest number of true positives (i.e. 140) from the PubChem dataset so far, as compared to other published models, and can potentially serve as a basis for the prediction of hERG active compounds. Validating this model against FDA-withdrawn substances indicated that it may even be useful for differentiating between mechanisms underlying QT prolongation.

  • 191. Chavan, Swapnil
    et al.
    Friedman, Ran
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy2015Inngår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 16, nr 5, s. 11659-11677Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity.

  • 192. Chavan, Swapnil
    et al.
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Karlsson, Bjorn C. G.
    Rosengren, Annika M.
    Ballabio, Davide
    Consonni, Viviana
    Todeschini, Roberto
    Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study2014Inngår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, nr 10, s. 18162-18174Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  • 193.
    Chen, Moashan
    et al.
    LaTrobeUniversity.
    Hongxing, Zhao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    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.
    Data on the expression of cellular lncRNAs in human adenovirus infected cells2016Inngår i: Data in Brief, E-ISSN 2352-3409, Vol. 8, s. 1263-1279Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Expression of cellular long non-coding RNAs (lncRNAs) in human primary lung fibroblasts (IMR-90) during the course of adenovirus type 2 (Ad2) infection was studied by strand-specific whole transcriptome sequencing. In total, 645 cellular lncRNAs were expressed at a significant level and 398 of them were changed more than 2-fold. The changes in expression followed a distinct temporal pattern. Significantly, 80% of the changes occurred at the late phase and 80% of the de-regulated lncRNAs were up-regulated. The three largest groups of deregulated lncRNAs were 125 antisense RNAs, 111 pseudogenes and 85 long intergenic non-coding RNAs (lincRNAs). Lastly, more than 36% of lncRNAs have been shown to interact with RNA binding proteins.

  • 194.
    Cho, S. Ei
    et al.
    Stanford Univ, Biol, Stanford, CA USA.
    Roy, J.
    Stanford Univ, Biol, Stanford, CA USA.
    Ivarsson, Ylva
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Cyert, M. S.
    Stanford Univ, Biol, Stanford, CA USA.
    Investigating the phospho-regulation of ER shaping protein RTN1A (Reticulon-1A) by the Calcineurin phosphatase.2017Inngår i: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 28, nr 26, s. 3727-3727Artikkel i tidsskrift (Annet vitenskapelig)
  • 195.
    Chowdhury, Azazul Islam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hörnaeus, Katarina
    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.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala Univ, Med Cell Biol, Uppsala, Sweden..
    Role of PIAS1 in palmitate mediated beta cell dysfunction2015Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S230-S230Artikkel i tidsskrift (Annet vitenskapelig)
  • 196.
    Chowdhury, Azazul Islam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hörnaeus, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Role of PIAS1 in palmitate-mediated beta-cell dysfunctionManuskript (preprint) (Annet vitenskapelig)
  • 197.
    Chowdhury, Azazul
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Satagopam, Venkata P.
    Manukyan, Levon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Artemenko, Konstantin A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fung, Yi Man Eva
    Schneider, Reinhard
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Signaling in Insulin-Secreting MIN6 Pseudoislets and Monolayer Cells2013Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 12, nr 12, s. 5954-5962Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cell cell interactions are of fundamental importance for cellular function. In islets of Langerhans, which control blood glucose levels by secreting insulin in response to the blood . glucose concentration, the secretory response of intact islets is c higher than that of insulin-producing beta-cells not arranged in the islet architecture. The objective was to define mechanisms by which cellular performance is enhanced when cells are arranged in a) three-dimensional space. The task was addressed by making a c comprehensive analysis based on protein expression patterns " generated from insulin-secreting MIN6 cells grown as islet-like c clusters, so-called pseudoislets, and in monolayers. After culture, glucose-stimulated insulin secretion (GSIS) was measured from monolayers and pseudoislets. GSIS rose 6-fold in pseudoislets but only 3-fold in monolayers when the glucose concentration was increased from 2 to 20 mmol/L. Proteins from pseudoislets and monolayers were extracted and analyzed by liquid-chromatography mass spectrometry, and differentially expressed proteins were mapped onto KEGG pathways. Protein profiling identified 1576 proteins, which were common to pseudoislets and monolayers. When mapped onto KEGG pathways, 11 highly enriched pathways were identified. On the basis of differences in expression of proteins belonging to the pathways in pseudoislets and monolayers, predictions of differential pathway activation were performed. Mechanisms enhancing insulin secretory capacity of the beta-cell, when situated in the islet, include pathways regulating glucose metabolism, cell interaction, and translational regulation.

  • 198.
    Christopeit, Tony
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Protein Interaction Studies with Low Molecular Weight Ligands: Applications for Drug Discovery, Basic Research and Diagnostic Tool Design2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In this thesis, the interactions between different proteins and small ligands were characterized by surface plasmon resonance spectroscopy (SPR) and fluorescence resonance energy transfer (FRET) based assays.   

    For the C-reactive protein (CRP), a new type of artificial binder was identified which allows designing diagnostic assays superior to commonly used standard assays. Furthermore, an interaction study with the endogenous ligand phosphocholine revealed the importance of the avidity of pentameric CRP for the distinction of different types of lipid membranes. The interaction study with calcium showed how SPR based assays can be used to study ion-protein interactions despite the low atomic weight of ions.   

    The transmembrane protease BACE1, an important drug target for Alzheimer’s disease, was immobilized to an SPR biosensor surface and embedded into a lipid membrane. An interaction study with a set of known BACE1 inhibitors showed that the transmembrane region has only minor effects on the interactions. Furthermore the pH-dependencies of the interactions were investigated and revealed new important conclusions for inhibitor design. Computer aided modelling showed that the protonation state of the aspartic dyad is dependent on the interacting inhibitor which offers new perspectives for in silico screenings.

    The SPR assay developed for BACE1 was adapted to a more complex membrane protein, the pentameric β3 GABAA receptor. The assay allowed the pharmacological characterisation for histaminergic and GABAergic ligands and gave further evidence for cross-talk between the two signal transduction pathways. This study shows that the immobilisation method used for BACE1 and the ß3 GABAA receptor has the potential to become a standard method for handling membrane proteins.  

    The identification of new drug leads from natural sources is a common strategy for drug discovery. A combination of SPR and FRET based activity assays were explored to increase the efficiency of this process. For HIV-1 protease, secreted aspartic protease (SAP) 1, 2 and 3 extracts from a marine vertebrate were identified containing potent inhibitors which interacted with the active site of the enzymes.

    The studies in this thesis show that the investigation of protein interactions is crucial for understanding protein functions and can help to develop novel drugs for the treatment of different diseases.

    Delarbeid
    1. Powerful protein binders from designed polypeptides and small organic molecules: a general concept for protein recognition
    Åpne denne publikasjonen i ny fane eller vindu >>Powerful protein binders from designed polypeptides and small organic molecules: a general concept for protein recognition
    Vise andre…
    2011 (engelsk)Inngår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 50, nr 8, s. 1823-1827Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    High-affinity binders for the C-reactive protein (CRP), with dissociation constants in the pM to nM range and selectivities in human serum comparable to those of antibodies, were obtained by conjugation of 16 designed polypeptides to phosphocholine, a small molecule that binds CRP with a KDvalue of 5I . The polypeptides were not designed specifically to recognize CRP and bind by an adapted fit mechanism.

    Emneord
    bioorganic chemistry, C-reactive protein, phosphocholine, polypeptides, proteins
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-147682 (URN)10.1002/anie.201005059 (DOI)000287836200012 ()21328648 (PubMedID)
    Tilgjengelig fra: 2011-02-27 Laget: 2011-02-27 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. Characterization of Ca2+ and phosphocholine interactions with C-reactive protein using a surface plasmon resonance biosensor
    Åpne denne publikasjonen i ny fane eller vindu >>Characterization of Ca2+ and phosphocholine interactions with C-reactive protein using a surface plasmon resonance biosensor
    2009 (engelsk)Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 391, nr 1, s. 39-44Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The interactions between Ca2+ and C-reactive protein (CRP) have been characterized using a surface plasmon resonance (SPR) biosensor. The protein was immobilized on a sensor chip, and increasing concentrations of Ca2+ or phosphocholine were injected. Binding of Ca2+ induced a 10-fold higher signal than expected from the molecular weight of Ca2+. It was interpreted to result from the conformational change that occurs on binding of Ca2+. Two sites with different characteristics were distinguished: a high-affinity site with K-D = 0.03 mM and a low-affinity site with K-D = 5.45 mM. The pH dependencies of the two Ca2+ interactions were different and enabled the assignment of the different sites in the three-dimensional structure of CRP. There was no evidence for cooperativity in the phosphocholine interaction, which had K-D = 5 mu M at 10 mM Ca2+. SPR biosensors can clearly detect and quantify the binding of very small molecules or ions to immobilized proteins despite the theoretically very low signals expected on binding, provided that significant conformational changes are involved. Both the interactions and the conformational changes can be characterized. The data have important implications for the understanding of the function of CRP and Suggest that Ca2+ is an efficient regulator under physiological conditions.

    Emneord
    C-reactive protein (CRP); Calcium binding; SPR biosensor, Conformational change, pH dependency, Phosphocholine
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-128986 (URN)10.1016/j.ab.2009.04.037 (DOI)000267063200006 ()19435596 (PubMedID)
    Tilgjengelig fra: 2010-08-05 Laget: 2010-08-05 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3. Effect of the Protonation State of the Titratable Residues on the Inhibitor Affinity to BACE-1
    Åpne denne publikasjonen i ny fane eller vindu >>Effect of the Protonation State of the Titratable Residues on the Inhibitor Affinity to BACE-1
    Vise andre…
    2010 (engelsk)Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 49, nr 34, s. 7255-7263Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACE-1 is one of the aspartic proteases involved in the cleavage of beta amyloid peptide, an initial step in the formation of amyloid plaques whose toxicity induces neuron death in Alzheimer's disease patients. One of the central issues in the search of novel BACE-1 inhibitors is the optimum pH for the binding of inhibitors to the enzyme. It is known that the enzyme has optimal catalytic activity at acidic pH, while cell active inhibitors may bind optimally at higher pH. In this work we determine the effect of the pH on the affinities of a set of inhibitors, with a variety of chemical motifs, for the ectodomain region of BACE-1 by a surface plasmon resonance (SPR) biosensor based assay. In order to understand the molecular interactions that underlie the diverse optimum pH for the binding of the various inhibitors as observed experimentally, we have calculated the titration curves for a set of BACE-1 ligand complexes. The results indicate that the pK(a) values of the titratable residues of the protein depend on the nature of the ligand involved, in disagreement with previous work. The enzyme-inhibitor structures with the resulting protonation states at pH values 4.5 and 7.4 served as the starting point for the prediction of the pH-dependent binding ranking. Our calculations reproduced the entire affinity ranking observed upon pH increase and most of the binding trends among inhibitors, especially at low pH. Finally, our cell-based assays indicate a possible correlation between high inhibitor affinity at both acidic and neutral pH values, with optimal cell response, a result that may open new venues for the search of potent BACE-1 inhibitors that are active at the cellular level.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-129426 (URN)10.1021/bi100637n (DOI)000281052600003 ()20687525 (PubMedID)
    Tilgjengelig fra: 2010-08-15 Laget: 2010-08-15 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    4. A surface plasmon resonance-based biosensor with full-length BACE1 in a reconstituted membrane
    Åpne denne publikasjonen i ny fane eller vindu >>A surface plasmon resonance-based biosensor with full-length BACE1 in a reconstituted membrane
    Vise andre…
    2011 (engelsk)Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 414, nr 1, s. 14-22Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A surface plasmon resonance (SPR) biosensor-based assay for membrane-embedded full-length BACE1 (β-site amyloid precursor protein cleaving enzyme 1), a drug target for Alzheimer's disease, has been developed. It allows the analysis of interactions with the protein in its natural lipid membrane environment. The enzyme was captured via an antibody recognizing a C-terminal His6 tag, after which a lipid membrane was reconstituted on the chip using a brain lipid extract. The interaction between the enzyme and several inhibitors confirmed that the surface was functional. It had slightly different interaction characteristics as compared with a reference surface with immobilized ectodomain BACE1 but had the same inhibitor characteristic pH effect. The possibility of studying interactions with BACE1 under more physiological conditions than assays using truncated enzyme or conditions dictated by high enzyme activity is expected to increase our understanding of the role of BACE1 in Alzheimer's disease and contribute to the discovery of clinically efficient BACE1 inhibitors. The strategy exploited in the current study can be adapted to other membrane-bound drug targets by selecting suitable capture antibodies and lipid mixtures for membrane reconstitution.

    Emneord
    BACE1, beta-Secretase, Biosensor, Surface plasmon resonance, SPR, Enzyme, Inhibitor, Membrane reconstitution, Membrane enzyme, Alzheimer's disease
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-153630 (URN)10.1016/j.ab.2011.02.041 (DOI)000290704300003 ()21382336 (PubMedID)
    Tilgjengelig fra: 2011-05-16 Laget: 2011-05-16 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    5. Histaminergic pharmacology of homo-oligomeric beta 3 gamma-aminobutyric acid type A receptors characterized by surface plasmon resonance biosensor technology
    Åpne denne publikasjonen i ny fane eller vindu >>Histaminergic pharmacology of homo-oligomeric beta 3 gamma-aminobutyric acid type A receptors characterized by surface plasmon resonance biosensor technology
    Vise andre…
    2012 (engelsk)Inngår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 84, nr 3, s. 341-351Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A surface plasmon resonance biosensor assay was established for studying the interactions of 51 histaminergic and 15 GABAergic ligands with homo-oligomeric beta 3 GABA(A) receptors. Detergent solubilized receptors were successfully immobilized via affinity-capture on biosensor surfaces. The interaction kinetics of both histaminergic and GABAergic ligands were very rapid but affinities could be determined by steady-state analysis. Binding of several GABAergic ligands was observed, in agreement with previous data. Histamine and 16 histaminergic ligands were detected to directly bind to beta 3 GABA(A) receptors with micromolar affinity (K-D <300 mu M), thus extending previous evidence that beta 3 GABA(A) receptors can interact with histaminergic ligands. Histamine exhibited an affinity for these receptors comparable to that for human histamine type 1 (H1) or type 2 (H2) receptors. Furthermore, 13 of these histaminergic ligands appeared to compete with histamine. The discovery that H2, H3 and H4 receptor ligands interact with beta 3 receptors indicates a unique histaminergic pharmacology of these receptors. Due to their low affinity for the homo-pentameric beta 3 receptors these histaminergic drugs are not expected to modulate these receptors at clinically relevant concentrations. The results support the use of the new biosensor assay for the identification of drugs interacting with full length receptors and for fragment-based drug discovery of high affinity ligands for beta 3 receptors. Drugs with high affinity and selectivity for these receptors can be used to clarify the question whether beta 3 receptors do exist in the brain, and provide new avenues for the development of therapeutically active compounds targeting this novel histamine binding site. 

    Emneord
    Ligand-gated ion channel, gamma-Aminobutyric acid type A receptor, Histamine, Surface plasmon resonance, Competition analysis
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-177842 (URN)10.1016/j.bcp.2012.04.008 (DOI)000305546200011 ()
    Tilgjengelig fra: 2012-07-20 Laget: 2012-07-19 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    6. Corrigendum to "Histaminergic pharmacology of homo-oligomeric β3 γ-aminobutyric acid type A receptors characterized by surface plasmon resonance biosensor technology" (Biochemical Pharmacology (2012) 84 (341-351))
    Åpne denne publikasjonen i ny fane eller vindu >>Corrigendum to "Histaminergic pharmacology of homo-oligomeric β3 γ-aminobutyric acid type A receptors characterized by surface plasmon resonance biosensor technology" (Biochemical Pharmacology (2012) 84 (341-351))
    Vise andre…
    2012 (engelsk)Inngår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 84, nr 11, s. 1541-Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-187955 (URN)10.1016/j.bcp.2012.09.013 (DOI)000311465900017 ()
    Tilgjengelig fra: 2012-12-12 Laget: 2012-12-12 Sist oppdatert: 2017-05-03bibliografisk kontrollert
    7. Efficient Screening of Marine Extracts for Protease Inhibitors by Combining FRET Based Activity Assays and Surface Plasmon Resonance Spectroscopy Based Binding Assays
    Åpne denne publikasjonen i ny fane eller vindu >>Efficient Screening of Marine Extracts for Protease Inhibitors by Combining FRET Based Activity Assays and Surface Plasmon Resonance Spectroscopy Based Binding Assays
    2013 (engelsk)Inngår i: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 11, nr 11, s. 4279-4293Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the screening process is the generation of false positive hits through unspecific effects from the complex chemical composition of the crude extracts. In this study, we explored a combination of a fluorescence resonance energy transfer (FRET) based activity assay and a surface plasmon resonance (SPR) based binding assay to avoid this problem. An aqueous extract was prepared from rest raw material of the Norwegian spring spawning herring, and further fractionated by methanol solubility and solid phase extraction. FRET based activity assays were used to determine the influence of each extract on the activity of different proteases. Several extracts showed more than 50% inhibition. The inhibition mechanisms were elucidated by SPR based competition experiments with known inhibitors. For the secreted aspartic proteases 1, 2, 3 and HIV-1 protease, the results indicated that some extracts contain inhibitors interacting specifically with the active site of the enzymes. The study shows that a combination of an activity assay and an SPR based binding assay is a powerful tool to identify potent inhibitors in marine extracts. Furthermore, the study shows that marine vertebrates offer an interesting source for new bioactive compounds, although they have rarely been explored for this purpose.

    HSV kategori
    Forskningsprogram
    Biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-188327 (URN)10.3390/md11114279 (DOI)000330521400010 ()
    Tilgjengelig fra: 2012-12-14 Laget: 2012-12-14 Sist oppdatert: 2017-12-06bibliografisk kontrollert
  • 199.
    Christopeit, Tony
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Øverbø, Kersti
    Nofima AS, Tromsø, Norway.
    Danielson, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Nilsen, Inge W.
    Nofima AS, Tromsø, Norway.
    Efficient Screening of Marine Extracts for Protease Inhibitors by Combining FRET Based Activity Assays and Surface Plasmon Resonance Spectroscopy Based Binding Assays2013Inngår i: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 11, nr 11, s. 4279-4293Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the screening process is the generation of false positive hits through unspecific effects from the complex chemical composition of the crude extracts. In this study, we explored a combination of a fluorescence resonance energy transfer (FRET) based activity assay and a surface plasmon resonance (SPR) based binding assay to avoid this problem. An aqueous extract was prepared from rest raw material of the Norwegian spring spawning herring, and further fractionated by methanol solubility and solid phase extraction. FRET based activity assays were used to determine the influence of each extract on the activity of different proteases. Several extracts showed more than 50% inhibition. The inhibition mechanisms were elucidated by SPR based competition experiments with known inhibitors. For the secreted aspartic proteases 1, 2, 3 and HIV-1 protease, the results indicated that some extracts contain inhibitors interacting specifically with the active site of the enzymes. The study shows that a combination of an activity assay and an SPR based binding assay is a powerful tool to identify potent inhibitors in marine extracts. Furthermore, the study shows that marine vertebrates offer an interesting source for new bioactive compounds, although they have rarely been explored for this purpose.

  • 200. Chu, Dinh-Toi
    et al.
    Nguyet, Nguyen Thi Minh
    Nga, Vu Thi
    Lien, Nguyen Vu Thai
    Vo, Duc Duy
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Lien, Nguyen
    Ngoc, Vo Truong Nhu
    Son, Le Hoang
    Le, Duc-Hau
    Nga, Vu Bich
    Tu, Pham Van
    To, Ta Van
    Ha, Luu Song
    Vietnam Womens Acad, Hanoi, Vietnam.
    Tao, Yang
    Nanjing Agr Univ, Coll Food Sci & Technol, Nanjing 210095 8, Jiangsu, Peoples R China.
    Pham, Van-Huy
    An update on obesity: Mental consequences and psychological interventions2019Inngår i: Diabetes & Metabolic syndrome: clinical Research & Reviews, ISSN 1871-4021, E-ISSN 1878-0334, Vol. 13, nr 1, s. 155-160Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Besides physical consequences, obesity has negative psychological effects, thereby lowering human life quality. Major psychological consequences of this disorder includes depression, impaired body image, low self-esteem, eating disorders, stress and poor quality of life, which are correlated with age and gender. Physical interventions, mainly diet control and energy balance, have been widely applied to treat obesity; and some psychological interventions including behavioral therapy, cognitive behavioral therapy and hypnotherapy have showed some effects on obesity treatment. Other psychological therapies, such as relaxation and psychodynamic therapies, are paid less attention. This review aims to update scientific evidence regarding the mental consequences and psychological interventions for obesity. (c) 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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