uu.seUppsala universitets publikationer
Ändra sökning
Avgränsa sökresultatet
1234567 1 - 50 av 1311
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Abbas, Alaa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Palladium-Catalysed Carbonylative Synthesis of Acylamidines2014Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 2.
    Abdurakhmanov, Eldar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Discovery and evaluation of direct acting antivirals against hepatitis C virus2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Until recently, the standard therapy for hepatitis C treatment has been interferon and ribavirin. Such treatment has only 50% efficacy and is not well tolerated. The emergence of new drugs has increased the treatment efficacy to 90%. Despite such an achievement, the success is limited since the virus mutates rapidly, causing the emergence of drug resistant forms. In addition, most new drugs were developed to treat genotype 1 infections. Thus, development of new potent antivirals is needed and drug discovery against hepatitis C is continued.

    In this thesis, a FRET-based protease assay was used to evaluate new pyrazinone based NS3 protease inhibitors that are structurally different to the newly approved and currently developing drugs. Several compounds in this series showed good potencies in the nanomolar range against NS3 proteases from genotype 1, 3, and the drug resistance variant R155K. We assume that these compounds can be further developed into drug candidates that possess activity against above mentioned enzyme variants.

    By using SPR technology, we analyzed interaction mechanisms and characteristics of allosteric inhibitors targeting NS5B polymerases from genotypes 1 and 3. The compounds exhibited different binding mechanisms and displayed a low affinity against NS5B from genotype 3.

    In order to evaluate the activity and inhibitors of the NS5B polymerase, we established an SPR based assay, which enables the monitoring of polymerization and its inhibition in real time. This assay can readily be implemented for the discovery of inhibitors targeting HCV.

    An SPR based fragment screening approach has also been established. A screen of a fragment library has been performed in order to identify novel scaffolds that can be used as a starting point for development of new allosteric inhibitors against NS5B polymerase. Selected fragments will be further elaborated to generate a new potent allosteric drug candidate.

    Alternative approaches have successfully been developed and implemented to the discovery of potential lead compounds targeting two important HCV drug targets.

    Delarbeten
    1. Discovery of pyrazinone based compounds that potently inhibit the drug resistant enzyme variant R155K of the hepatitis C virus NS3 protease
    Öppna denna publikation i ny flik eller fönster >>Discovery of pyrazinone based compounds that potently inhibit the drug resistant enzyme variant R155K of the hepatitis C virus NS3 protease
    Visa övriga...
    2016 (Engelska)Ingår i: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 24, nr 12, s. 2603-2620Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors with variations in the C-terminus. Biochemical evaluation was performed using genotype 1a, both the wildtype and the drug resistant enzyme variant, R155K. Surprisingly, compounds without an acidic sulfonamide retained good inhibition, challenging our previous molecular docking model. Moreover, selected compounds in this series showed nanomolar potency against R155K NS3 protease; which generally confer resistance to all HCV NS3 protease inhibitors approved or in clinical trials. These results further strengthen the potential of this novel substance class, being very different to the approved drugs and clinical candidates, in the development of inhibitors less sensitive to drug resistance.

    Nyckelord
    Hepatitis C virus; Drug resistance; Pyrazinone; NS3 protease inhibitors; R155K
    Nationell ämneskategori
    Organisk kemi
    Forskningsämne
    Läkemedelskemi
    Identifikatorer
    urn:nbn:se:uu:diva-243315 (URN)10.1016/j.bmc.2016.03.066 (DOI)000376727800002 ()27160057 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, D0571301
    Tillgänglig från: 2015-02-08 Skapad: 2015-02-08 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
    2. Pyrazinone based hepatitis C virus NS3 protease inhibitors targeting genotype 1a, 3a and the drug-resistant enzyme variant R155K
    Öppna denna publikation i ny flik eller fönster >>Pyrazinone based hepatitis C virus NS3 protease inhibitors targeting genotype 1a, 3a and the drug-resistant enzyme variant R155K
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-265295 (URN)
    Tillgänglig från: 2015-10-26 Skapad: 2015-10-26 Senast uppdaterad: 2016-01-13
    3. Resolution of the Interaction Mechanisms and Characteristics of Non-nucleoside Inhibitors of Hepatitis C Virus Polymerase - Laying the Foundation for Discovery of Allosteric HCV Drugs
    Öppna denna publikation i ny flik eller fönster >>Resolution of the Interaction Mechanisms and Characteristics of Non-nucleoside Inhibitors of Hepatitis C Virus Polymerase - Laying the Foundation for Discovery of Allosteric HCV Drugs
    Visa övriga...
    2013 (Engelska)Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 97, nr 3, s. 356-368Artikel i tidskrift (Övrigt vetenskapligt) Published
    Abstract [en]

    Development of allosteric inhibitors into efficient drugs is hampered by their indirect mode-of-action and complex structure-kinetic relationships. To enablethe design of efficient allosteric drugs targeting the polymerase of hepatitis C virus(NS5B), the interaction characteristics of three non-nucleoside compounds (filibuvir, VX-222, and tegobuvir) inhibiting HCV replication via NS5B have been analyzed. Since there was no logical correlation between the anti-HCV replicative and enzyme inhibitory effects of the compounds, surface plasmon resonance biosensor technology was used to resolve the mechanistic, kinetic, thermodynamic and chemodynamic features of their interactions with their target and their effect on itsinteraction with RNA. Tegobuvir could not be seen to interact with NS5B at all while filibuvir interacted in a single reversible step (except at low temperatures) and VX-222 in two serial steps, interpreted as an induced fit mechanism. Both filibuvir and VX-222 interfered with the interaction between NS5B and RNA. They competed for binding to the enzyme, suggesting that they had a common inhibition mechanism and identical or overlapping binding sites. The greater anti-HCV replicative activityof VX-222 over filibuvir is hypothesized to be due to a greater allosteric conformational effect, resulting in the formation of a less catalytically competent complex. In addition, the induced fit mechanism of VX-222 gives it a kinetic advantage over filibuvir, exhibited as a longer residence time. These insights have important consequences for the selection and optimization of new allosteric NS5Binhibitors.

    Nyckelord
    HCV, NS5B, filibuvir, VX-222, tegobuvir, allosteric inhibitor, induced fit, kinetics, chemodynamics, thermodynamics
    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Forskningsämne
    Biokemi; Biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-171996 (URN)10.1016/j.antiviral.2012.12.027 (DOI)000317709400018 ()
    Tillgänglig från: 2012-04-03 Skapad: 2012-03-31 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    4. Characterization of allosteric inhibitors of hepatitis C virus polymerase – a genotype comparative study
    Öppna denna publikation i ny flik eller fönster >>Characterization of allosteric inhibitors of hepatitis C virus polymerase – a genotype comparative study
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-265287 (URN)
    Tillgänglig från: 2015-10-26 Skapad: 2015-10-26 Senast uppdaterad: 2016-01-13
    5. A time-resolved surface plasmon resonance based hepatitis C virus NS5B polymerase assay and its application for drug discovery
    Öppna denna publikation i ny flik eller fönster >>A time-resolved surface plasmon resonance based hepatitis C virus NS5B polymerase assay and its application for drug discovery
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-265290 (URN)
    Tillgänglig från: 2015-10-26 Skapad: 2015-10-26 Senast uppdaterad: 2016-01-13
    6. Fragment library screening addressing Hepatitis C protein NS5B from genotypes 1 and 3 using an SPR-based approach
    Öppna denna publikation i ny flik eller fönster >>Fragment library screening addressing Hepatitis C protein NS5B from genotypes 1 and 3 using an SPR-based approach
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-265292 (URN)
    Tillgänglig från: 2015-10-26 Skapad: 2015-10-26 Senast uppdaterad: 2016-01-13
  • 3.
    Abdurakhmanov, Eldar
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Solbak, Sara
    Danielson, Helena
    Characterization of allosteric inhibitors of hepatitis C virus polymerase – a genotype comparative studyManuskript (preprint) (Övrigt vetenskapligt)
  • 4.
    Abdurakhmanov, Eldar
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Solbak, Sara Oie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Danielson, U. Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Biophysical Mode-of-Action and Selectivity Analysis of Allosteric Inhibitors of Hepatitis C Virus (HCV) Polymerase2017Ingår i: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 9, nr 6, artikel-id 151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allosteric inhibitors of hepatitis C virus (HCV) non-structural protein 5B (NS5B) polymerase are effective for treatment of genotype 1, although their mode of action and potential to inhibit other isolates and genotypes are not well established. We have used biophysical techniques and a novel biosensor-based real-time polymerase assay to investigate the mode-of-action and selectivity of four inhibitors against enzyme from genotypes 1b (BK and Con1) and 3a. Two thumb inhibitors (lomibuvir and filibuvir) interacted with all three NS5B variants, although the affinities for the 3a enzyme were low. Of the two tested palm inhibitors (dasabuvir and nesbuvir), only dasabuvir interacted with the 1b variant, and nesbuvir interacted with NS5B 3a. Lomibuvir, filibuvir and dasabuvir stabilized the structure of the two 1b variants, but not the 3a enzyme. The thumb compounds interfered with the interaction between the enzyme and RNA and blocked the transition from initiation to elongation. The two allosteric inhibitor types have different inhibition mechanisms. Sequence and structure analysis revealed differences in the binding sites for 1b and 3a variants, explaining the poor effect against genotype 3a NS5B. The indirect mode-of-action needs to be considered when designing allosteric compounds. The current approach provides an efficient strategy for identifying and optimizing allosteric inhibitors targeting HCV genotype 3a.

  • 5.
    Ablikim, M.
    et al.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Achasov, M. N.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia..
    Ahmed, S.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Ai, X. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Albayrak, O.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Albrecht, M.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Ambrose, D. J.
    Univ Rochester, Rochester, NY 14627 USA..
    Amoroso, A.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia.;Helmholtz Inst Mainz, D-55099 Mainz, Germany.;Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany.;Chinese Acad Sci, Beijing 100049, Peoples R China.;Univ Hawaii, Honolulu, HI 96822 USA.;Univ Punjab, Lahore 54590, Pakistan.;Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    An, F. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    An, Q.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Bai, J. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ferroli, R. Baldini
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Ban, Y.
    Peking Univ, Beijing 100871, Peoples R China..
    Bennett, D. W.
    Indiana Univ, Bloomington, IN 47405 USA..
    Bennett, J. V.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Berger, N. B.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Bertani, M.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Bettoni, D.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Bian, J. M.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Bianchi, F.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Boger, E.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Boyko, I.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Briere, R. A.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Cai, H.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Cai, X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Cakir, O.
    Ankara Univ, TR-06100 Ankara, Turkey..
    Calcaterra, A.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy.;Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany.;Chinese Acad Sci, Beijing 100049, Peoples R China.;Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Cao, G. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Cetin, S. A.
    Istanbul Bilgi Univ, TR-34060 Istanbul, Turkey..
    Chang, J. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chelkov, G.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Chen, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, H. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, H. Y.
    Beihang Univ, Beijing 100191, Peoples R China..
    Chen, J. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, M. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, S.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Chen, S. J.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Chen, X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Chen, X. R.
    Lanzhou Univ, Lanzhou 730000, Peoples R China..
    Chen, Y. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Cheng, H. P.
    Huangshan Coll, Huangshan 245000, Peoples R China..
    Chu, X. K.
    Peking Univ, Beijing 100871, Peoples R China..
    Cibinetto, G.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Dai, H. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dai, J. P.
    Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China..
    Dbeyssi, A.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Dedovich, D.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Deng, Z. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Denig, A.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Denysenko, I.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Destefanis, M.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    De Mori, F.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Ding, Y.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Dong, C.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Dong, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dong, L. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dong, M. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Dou, Z. L.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Du, S. X.
    Zhengzhou Univ, Zhengzhou 450001, Peoples R China..
    Duan, P. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Fan, J. Z.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Fang, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Fang, S. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Fang, X.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Fang, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Farinelli, R.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy.;Univ Ferrara, I-44122 Ferrara, Italy..
    Fava, L.
    Univ Piemonte Orientale, I-15121 Alessandria, Italy.;INFN, I-10125 Turin, Italy..
    Fedorov, O.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Feldbauer, F.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Felici, G.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Feng, C. Q.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Fioravanti, E.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Fritsch, M.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany.;Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Fu, C. D.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gao, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gao, X. L.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Gao, X. Y.
    Beihang Univ, Beijing 100191, Peoples R China..
    Gao, Y.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Gao, Z.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Garzia, I.
    INFN, Sez Ferrara, I-44122 Ferrara, Italy..
    Goetzen, K.
    GSI Helmholtzcentre Heavy Ion Res GmbH, D-64291 Darmstadt, Germany..
    Gong, L.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Gong, W. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gradl, W.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Greco, M.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Gu, M. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Gu, Y. T.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Guan, Y. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, A. Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, L. B.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Guo, R. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Guo, Y. P.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Haddadi, Z.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Hafner, A.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Han, S.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Hao, X. Q.
    Henan Normal Univ, Xinxiang 453007, Peoples R China..
    Harris, F. A.
    Univ Hawaii, Honolulu, HI 96822 USA..
    He, K. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Heinsius, F. H.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Held, T.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Heng, Y. K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Holtmann, T.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Hou, Z. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Hu, C.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Hu, H. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Hu, J. F.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Hu, T.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Hu, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Huang, G. S.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Huang, J. S.
    Henan Normal Univ, Xinxiang 453007, Peoples R China..
    Huang, X. T.
    Shandong Univ, Jinan 250100, Peoples R China..
    Huang, X. Z.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Huang, Y.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Huang, Z. L.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Hussain, T.
    Univ Punjab, Lahore 54590, Pakistan..
    Ji, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ji, Q. P.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Ji, X. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ji, X. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Jiang, L. W.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Jiang, X. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Jiang, X. Y.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Jiao, J. B.
    Shandong Univ, Jinan 250100, Peoples R China..
    Jiao, Z.
    Huangshan Coll, Huangshan 245000, Peoples R China..
    Jin, D. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Jin, S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Johansson, T
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Julin, A.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Kalantar-Nayestanaki, N.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Kang, X. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Kang, X. S.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Kavatsyuk, M.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Ke, B. C.
    Carnegie Mellon Univ, Pittsburgh, PA 15213 USA..
    Kiese, P.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Kliemt, R.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Kloss, B.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Kolcu, O. B.
    Istanbul Bilgi Univ, TR-34060 Istanbul, Turkey..
    Kopf, B.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Kornicer, M.
    Univ Hawaii, Honolulu, HI 96822 USA..
    Kupsc, Andrzej
    Uppsala universitet, The Svedberg-laboratoriet. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Kärnfysik.
    Khn, W.
    Justus Liebig Univ Giessen, Phys Inst 2, D-35392 Giessen, Germany..
    Lange, J. S.
    Justus Liebig Univ Giessen, Phys Inst 2, D-35392 Giessen, Germany..
    Lara, M.
    Indiana Univ, Bloomington, IN 47405 USA..
    Larin, P.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Leithoff, H.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Leng, C.
    INFN, I-10125 Turin, Italy..
    Li, Cui
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Kärnfysik.
    Li, Cheng
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Li, D. M.
    Zhengzhou Univ, Zhengzhou 450001, Peoples R China..
    Li, F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, F. Y.
    Peking Univ, Beijing 100871, Peoples R China..
    Li, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, H. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, H. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, J. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, Jin
    Seoul Natl Univ, Seoul 151747, South Korea..
    Li, K.
    Hangzhou Normal Univ, Hangzhou 310036, Peoples R China.;Shandong Univ, Jinan 250100, Peoples R China..
    Li, Lei
    Beijing Inst Petrochem Technol, Beijing 102617, Peoples R China..
    Li, P. R.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Li, Q. Y.
    Shandong Univ, Jinan 250100, Peoples R China..
    Li, T.
    Shandong Univ, Jinan 250100, Peoples R China..
    Li, W. D.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, W. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, X. L.
    Shandong Univ, Jinan 250100, Peoples R China..
    Li, X. M.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Li, X. N.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Li, X. Q.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Li, Y. B.
    Beihang Univ, Beijing 100191, Peoples R China..
    Li, Z. B.
    Sun Yat Sen Univ, Guangzhou 510275, Guangdong, Peoples R China..
    Liang, H.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liang, J. J.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Liang, Y. F.
    Sichuan Univ, Chengdu 610064, Peoples R China..
    Liang, Y. T.
    Justus Liebig Univ Giessen, Phys Inst 2, D-35392 Giessen, Germany..
    Liao, G. R.
    Guangxi Normal Univ, Guilin 541004, Peoples R China..
    Lin, D. X.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Liu, B.
    Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China..
    Liu, B. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, C. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, D.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liu, F. H.
    Shanxi Univ, Taiyuan 030006, Peoples R China..
    Liu, Fang
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, Feng
    Cent China Normal Univ, Wuhan 430079, Peoples R China..
    Liu, H. B.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Liu, H. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China.;Henan Univ Sci & Technol, Luoyang 471003, Peoples R China..
    Liu, H. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, J. B.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liu, J. P.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Liu, J. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, K.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Liu, K. Y.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Liu, L. D.
    Peking Univ, Beijing 100871, Peoples R China..
    Liu, P. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, Q.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Liu, S. B.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Liu, X.
    Lanzhou Univ, Lanzhou 730000, Peoples R China..
    Liu, Y. B.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Liu, Y. Y.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Liu, Z. A.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Liu, Zhiqing
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Loehner, H.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Lou, X. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lu, H. J.
    Huangshan Coll, Huangshan 245000, Peoples R China..
    Lu, J. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lu, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lu, Y. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Luo, C. L.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Luo, M. X.
    Zhejiang Univ, Hangzhou 310027, Zhejiang, Peoples R China..
    Luo, T.
    Univ Hawaii, Honolulu, HI 96822 USA..
    Luo, X. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Lyu, X. R.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Ma, F. C.
    Liaoning Univ, Shenyang 110036, Peoples R China..
    Ma, H. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, L. L.
    Shandong Univ, Jinan 250100, Peoples R China..
    Ma, M. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, Q. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, T.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, X. N.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Ma, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ma, Y. M.
    Shandong Univ, Jinan 250100, Peoples R China..
    Maas, F. E.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Maggiora, M.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Malik, Q. A.
    Univ Punjab, Lahore 54590, Pakistan..
    Mao, Y. J.
    Peking Univ, Beijing 100871, Peoples R China..
    Mao, Z. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Marcello, S.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Messchendorp, J. G.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Mezzadri, G.
    Univ Ferrara, I-44122 Ferrara, Italy..
    Min, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Mitchell, R. E.
    Indiana Univ, Bloomington, IN 47405 USA..
    Mo, X. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Mo, Y. J.
    Cent China Normal Univ, Wuhan 430079, Peoples R China..
    Morales, C. Morales
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Muchnoi, N. Yu.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia..
    Muramatsu, H.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Musiol, P.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Nefedov, Y.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Nerling, F.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Nikolaev, I. B.
    GI Budker Inst Nucl Phys SB RAS BINP, Novosibirsk 630090, Russia..
    Ning, Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Nisar, S.
    COMSATS Inst Informat Technol, Lahore 54000, Pakistan..
    Niu, S. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Niu, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Olsen, S. L.
    Seoul Natl Univ, Seoul 151747, South Korea..
    Ouyang, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Pacetti, S.
    INFN, I-06100 Perugia, Italy.;Univ Perugia, I-06100 Perugia, Italy..
    Pan, Y.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Patteri, P.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Pelizaeus, M.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Peng, H. P.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Peters, K.
    GSI Helmholtzcentre Heavy Ion Res GmbH, D-64291 Darmstadt, Germany..
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Ping, J. L.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Ping, R. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Poling, R.
    Univ Minnesota, Minneapolis, MN 55455 USA..
    Prasad, V.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qi, H. R.
    Beihang Univ, Beijing 100191, Peoples R China..
    Qi, M.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Qian, S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qiao, C. F.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Qin, L. Q.
    Shandong Univ, Jinan 250100, Peoples R China..
    Qin, N.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Qin, X. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qin, Z. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Qiu, J. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Rashid, K. H.
    Univ Punjab, Lahore 54590, Pakistan..
    Redmer, C. F.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Ripka, M.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Rong, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Rosner, Ch.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Ruan, X. D.
    Guangxi Univ, Nanning 530004, Peoples R China..
    Sarantsev, A.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Savrie, M.
    Univ Ferrara, I-44122 Ferrara, Italy..
    Schnier, C.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Schönning, Karin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Kärnfysik. Uppsala universitet, The Svedberg-laboratoriet.
    Schumann, S.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Shan, W.
    Peking Univ, Beijing 100871, Peoples R China..
    Shao, M.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Shen, C. P.
    Beihang Univ, Beijing 100191, Peoples R China..
    Shen, P. X.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Shen, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sheng, H. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Shi, M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Song, W. M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Song, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sosio, S.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Spataro, S.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Sun, G. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, J. F.
    Henan Normal Univ, Xinxiang 453007, Peoples R China..
    Sun, S. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, X. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, Y. J.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Sun, Y. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, Z. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Sun, Z. T.
    Indiana Univ, Bloomington, IN 47405 USA..
    Tang, C. J.
    Sichuan Univ, Chengdu 610064, Peoples R China..
    Tang, X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Tapan, I.
    Uludag Univ, TR-16059 Bursa, Turkey..
    Thorndike, E. H.
    Univ Rochester, Rochester, NY 14627 USA..
    Tiemens, M.
    Univ Groningen, KVI CART, NL-9747 AA Groningen, Netherlands..
    Uman, I.
    Near East Univ, Nicosia 10, Turkey..
    Varner, G. S.
    Univ Hawaii, Honolulu, HI 96822 USA..
    Wang, B.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Wang, B. L.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Wang, D.
    Peking Univ, Beijing 100871, Peoples R China..
    Wang, D. Y.
    Peking Univ, Beijing 100871, Peoples R China..
    Wang, K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, L. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, L. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, M.
    Shandong Univ, Jinan 250100, Peoples R China..
    Wang, P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, P. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, S. G.
    Peking Univ, Beijing 100871, Peoples R China..
    Wang, W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, W. P.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Wang, X. F.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Wang, Y.
    Soochow Univ, Suzhou 215006, Peoples R China..
    Wang, Y. D.
    Helmholtz Inst Mainz, D-55099 Mainz, Germany..
    Wang, Y. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, Y. Q.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Wang, Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, Z. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wang, Z. H.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Wang, Z. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Weber, T.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Wei, D. H.
    Guangxi Normal Univ, Guilin 541004, Peoples R China..
    Wei, J. B.
    Peking Univ, Beijing 100871, Peoples R China..
    Weidenkaff, P.
    Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany..
    Wen, S. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wiedner, U.
    Ruhr Univ Bochum, D-44780 Bochum, Germany..
    Wolke, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Kärnfysik.
    Wu, L. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wu, L. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Wu, Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xia, L.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Xia, L. G.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Xia, Y.
    Hunan Univ, Changsha 410082, Peoples R China..
    Xiao, D.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xiao, H.
    Univ South China, Hengyang 421001, Peoples R China..
    Xiao, Z. J.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Xie, Y. G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xiu, Q. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, G. F.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, J. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Xu, Q. J.
    Hangzhou Normal Univ, Hangzhou 310036, Peoples R China..
    Xu, Q. N.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Xu, X. P.
    Soochow Univ, Suzhou 215006, Peoples R China..
    Yan, L.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Yan, W. B.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Yan, W. C.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Yan, Y. H.
    Hunan Univ, Changsha 410082, Peoples R China..
    Yang, H. J.
    Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China..
    Yang, H. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yang, L.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Yang, Y. X.
    Guangxi Normal Univ, Guilin 541004, Peoples R China..
    Ye, M.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Ye, M. H.
    China Ctr Adv Sci & Technol, Beijing 100190, Peoples R China..
    Yin, J. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yu, B. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yu, C. X.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Yu, J. S.
    Lanzhou Univ, Lanzhou 730000, Peoples R China..
    Yuan, C. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yuan, W. L.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Yuan, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Yuncu, A.
    Istanbul Bilgi Univ, TR-34060 Istanbul, Turkey..
    Zafar, A. A.
    Univ Punjab, Lahore 54590, Pakistan..
    Zallo, A.
    INFN Lab Nazl Frascati, I-00044 I- Frascati, Italy..
    Zeng, Y.
    Hunan Univ, Changsha 410082, Peoples R China..
    Zeng, Z.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhang, B. X.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, B. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, C.
    Nanjing Univ, Nanjing 210093, Peoples R China..
    Zhang, C. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, D. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, H. H.
    Sun Yat Sen Univ, Guangzhou 510275, Guangdong, Peoples R China..
    Zhang, H. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, J. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, S. Q.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Zhang, X. Y.
    Shandong Univ, Jinan 250100, Peoples R China..
    Zhang, Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, Y. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhang, Y. N.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Zhang, Y. T.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhang, Yu
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Zhang, Z. H.
    Cent China Normal Univ, Wuhan 430079, Peoples R China..
    Zhang, Z. P.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhang, Z. Y.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Zhao, G.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, J. W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, J. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, J. Z.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Lei
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhao, Ling
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, M. G.
    Nankai Univ, Tianjin 300071, Peoples R China..
    Zhao, Q.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Q. W.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, S. J.
    Zhengzhou Univ, Zhengzhou 450001, Peoples R China..
    Zhao, T. C.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Y. B.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhao, Z. G.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhemchugov, A.
    Joint Inst Nucl Res, Dubna 141980, Moscow Region, Russia..
    Zheng, B.
    Univ South China, Hengyang 421001, Peoples R China..
    Zheng, J. P.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zheng, W. J.
    Shandong Univ, Jinan 250100, Peoples R China..
    Zheng, Y. H.
    Chinese Acad Sci, Beijing 100049, Peoples R China..
    Zhong, B.
    Nanjing Normal Univ, Nanjing 210023, Peoples R China..
    Zhou, L.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhou, X.
    Wuhan Univ, Wuhan 430072, Peoples R China..
    Zhou, X. K.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhou, X. R.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhou, X. Y.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, K.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, K. J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, S. H.
    Univ Sci & Technol Liaoning, Anshan 114051, Peoples R China..
    Zhu, X. L.
    Tsinghua Univ, Beijing 100084, Peoples R China..
    Zhu, Y. C.
    Univ Sci & Technol China, Hefei 230026, Peoples R China..
    Zhu, Y. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhu, Z. A.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zhuang, J.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zotti, L.
    Univ Turin, I-10125 Turin, Italy.;INFN, I-10125 Turin, Italy..
    Zou, B. S.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Zou, J. H.
    Inst High Energy Phys, Beijing 100049, Peoples R China..
    Amplitude analysis of D0 -> K -π+π+π-2017Ingår i: Physical Review D: covering particles, fields, gravitation, and cosmology, ISSN 2470-0010, E-ISSN 2470-0029, Vol. 95, nr 7, artikel-id 072010Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present an amplitude analysis of the decay D-0 -> K- pi(+)pi(+)pi(-) based on a data sample of 2.93 fb(-1) acquired by the BESIII detector at the psi(3770) resonance. With a nearly background free sample of about 16000 events, we investigate the substructure of the decay and determine the relative fractions and the phases among the different intermediate processes. Our amplitude model includes the two-body decays D-0 -> (K) over bar*(0)rho(0), D-0 -> K- a(1)(+) (1260) and D-0 -> K-1(-)(1270)pi(+), the three-body decays D-0 -> K-1(-)*(0)pi(+)pi(-) and D-0 -> K- pi(+)rho(0), as well as the four-body nonresonant decay D-0 -> K- pi(+)pi(+)pi(-). The dominant intermediate process is D-0 -> K(-)a(1)(+)(1260)accounting for a fit fraction of 54.6%.

  • 6.
    Abramsson, Mia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Production and characterization of Acetylcholine Binding Protein2018Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 7.
    Abu Hamdeh, Sami
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Shevchenko, Ganna
    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.
    Musunuri, Sravani
    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.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 6807Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.

  • 8.
    Abu Hamdeh, Sami
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Shevchenko, Ganna
    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.
    Musunuri, Sravani
    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.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Proteomic Differences Between Focal And Diffuse Traumatic Brain Injury In Human Brain Tissue2018Ingår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A238-A239Artikel i tidskrift (Övrigt vetenskapligt)
  • 9.
    Afifi, Hala
    et al.
    Institute of Pharmaceutical Science, King’s College London, UK.
    Karlsson, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Heenan, Richard K.
    ISIS-CCLRC, Rutherford Appleton Laboratory, Chilton, UK.
    Dreiss, Cécile A.
    Institute of Pharmaceutical Science, King’s College London, UK.
    Structural transitions in cholesterol-based wormlike micelles induced by encapsulating alkyl ester oils with varying architecture2012Ingår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 378, nr 1, s. 125-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The effect of encapsulating oils on the phase behaviour and the microstructure of wormlike micelles formed by polyoxyethylene cholesteryl ether (ChEO10) and triethylene glycol monododecyl ether co-surfactant (C12EO3) was investigated using rheology, Cryo-TEM and small-angle neutron scattering measurements. Six alkyl ester oils bearing small, systematic variations in their molecular structure were encapsulated: ethyl butyrate (EB24), ethyl caproate (ECO26), ethyl caprylate (EC28), methyl enanthate (ME17), methyl caprylate (MC18) and butyl butyrate (BB44), where the subscripts refer to the length of the alkyl chain and fatty acid chain, respectively, on either sides of the ester link. The addition of alkyl ester oils to ChEO10/C12EO3 solutions promotes the longitudinal growth of the surfactant aggregates into wormlike micelles possessing an elliptical cross-section, with rminor 31&#xa0;±&#xa0;2&#xa0;Å and rmajor varying from 45 to 70&#xa0;Å. At fixed alkyl chain length, oils with longer fatty acid chains were found to be more efficient in inducing wormlike micelle formation or their elongation, following the order: EC28&#xa0;&gt;&#xa0;ECO26&#xa0;&gt;&#xa0;EB24. Instead, at fixed fatty acid chain length, increasing the alkyl chain has a negative effect on the longitudinal micellar growth (MC18&#xa0;&gt;&#xa0;EC28 and EB24&#xa0;&gt;&#xa0;BB44). At high co-surfactant concentrations and in the presence of EB24, an unusual phase of ring-like micelles was detected. Overall, the orientation of the oil molecules within the micelles enables them to act as co-surfactants with a small head-group, decreasing the average cross-section area and promoting longitudinal growth of the micelles into worms.

  • 10.
    Agalo, Faith
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Synthesis of Insulin-Regulated Aminopeptidase (IRAP) inhibitors2015Självständigt arbete på avancerad nivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The need for alternative cognitive enhancers has risen due to the fact that clinical trial results of the drugs currently approved for treating these disorders have not been satisfactory.

    IRAP has become a possible drug target for treating cognitive impairment brought about by Alzheimer’s disease, head trauma or cerebral ischemia, among others. This came after the revelation that Angiotensin IV enhances memory and learning. Angiotensin IV, the endogenous ligand of IRAP has been structurally modified with the aim of producing potent IRAP inhibitors. However, the peptidic nature of these inhibitors restricts their use; they are not likely to cross the blood brain barrier.

    Other strategies for generating IRAP inhibitors have been through structure-based design and receptor based virtual screening. These drug-like molecules have exhibited positive results in animal studies.

    IRAP inhibitors have been identified via a HTS of 10500 low-molecular weight compounds to give the hit based on a spirooxindole dihydroquinazolinone scaffold, with an IC50 value of 1.5 µM. In this project, some analogues to this hit compound have successfully been synthesized using a known method, whereas others have been synthesized after additional method development.

    The application of the developed method was found to be limited, because poor yield was obtained when a compound with an electron withdrawing substituent on the aniline was synthesized. As a result of this, modification of this method may be required or new methods may have to be developed to synthesize these types of analogues.

    Inhibition capability of 5 new spirooxindole dihydroquinazolinones was tested through a biochemical assay. Compound 6e emerged as the most potent inhibitor in the series, with an IC50 value of 0.2 µM. This compound will now serve as a lead compound and should be used as a starting point for future optimization in order to generate more potent IRAP inhibitors.

     

  • 11.
    Agmo Hernández, Víctor
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Eriksson, Emma K.
    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.
    Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes2015Ingår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1848, nr 10, s. 2233-2243Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract Ubiquinone-10 is mostly known for its role as an electron and proton carrier in aerobic cellular respiration and its function as a powerful antioxidant. Accumulating evidence suggest, however, that this well studied membrane component could have several other important functions in living cells. The current study reports on a previously undocumented ability of ubiquinone-10 to modulate the mechanical strength and permeability of lipid membranes. Investigations of DPH fluorescence anisotropy, spontaneous and surfactant induced leakage of carboxyfluorescein, and interactions with hydrophobic and hydrophilic surfaces were used to probe the effects caused by inclusion of ubiquinone-10 in the membrane of phospholipid liposomes. The results show that ubiquinone in concentrations as low as 2&#xa0;mol.% increases the lipid packing order and condenses the membrane. The altered physicochemical properties result in a slower rate of release of hydrophilic components, and render the membrane more resistant towards rupture. As judged from comparative experiments using the polyisoprenoid alcohol solanesol, the quinone moiety is essential for the membrane stabilizing effects to occur. Our findings imply that the influence of ubiquinone-10 on the permeability and mechanical properties of phospholipid membranes is similar to that of cholesterol. The reported data indicate, however, that the molecular mechanisms are different in the two cases.

  • 12.
    Agmo Hernández, Víctor
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lendeckel, Uwe
    Institut für Medizinische Biochemie und Molekularbiologie, Universitätsmedizin Greifswald, Germany.
    Scholz, Fritz
    Institut für Biochemie, Universität Greifswald, Germany.
    Electrochemistry of Adhesion and Spreading of Lipid Vesicles on Electrodes2013Ingår i: Applications of Electrochemistry in Medicine / [ed] Schlesinger, Mordechay, Springer US , 2013, Vol. 56, s. 189-247Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    Biological membranes have developed to separate different compartments of organisms and cells. There is a large number of rather different functions which membranes have to fulfil: (1) they control the material and energy fluxes of metabolic processes, (2) they provide a wrapping protecting the compartments from chemical and physical attacks of the environment, (3) they provide interfaces at which specific biochemical machineries can operate (e.g., membrane bound enzymes), (4) they are equipped for signal transduction, (5) they possess the necessary stability and flexibility to allow cell division, and endo- and exocytosis as well as migration, (6) they present anchoring structures that enable cell-to-cell and cell-to-matrix physical interactions and intercellular communication. These are certainly not all functions of membranes as new functionalities are continuously reported. Since the biological membranes separate essentially aqueous solutions, such separating borders—if they should possess a reasonable stability and also flexibility combined with selective permeability—have to be built up of hydrophobic molecules exposing to both sides a similar interface. It was one of the most crucial and most lucky circumstances for the development and existence of life that certain amphiphilic molecules are able to assemble in bilayer structures (membranes), which—on one side—possess a rather high physical and chemical stability, and—on the other side—are able to incorporate foreign molecules for modifying both the physical properties as well as the permeability of the membranes for defined chemical species. The importance of the chemical function of membranes and all its constituents, e.g., ion channels, pore peptides, transport peptides, etc., is generally accepted. The fluid-mosaic model proposed by Singer and Nicolson [1] is still the basis to understand the biological, chemical, and physical properties of biological membranes. The importance of the purely mechanical properties of membranes came much later into the focus of research. The reasons are probably the dominance of biochemical thinking and biochemical models among biologists and medical researchers, as well as a certain lack of appropriate methods to probe mechanical properties of membranes. The last decades have changed that situation due to the development of techniques like the Atomic Force Microscopy, Fluorescence Microscopy, Micropipette Aspiration, Raman Microspectroscopy, advanced Calorimetry, etc. This chapter is aimed at elucidating how the properties of membranes can be investigated by studying the interaction of vesicles with a very hydrophobic surface, i.e., with the surface of a mercury electrode. This interaction is unique as it results in a complete disintegration of the bilayer membrane of the vesicles and the formation of an island of adsorbed lipid molecules, i.e., a monolayer island. This process can be followed by current-time measurements (chronoamperometry), which allow studying the complete disintegration process in all its details: the different steps of that disintegration can be resolved on the time scale and the activation parameters can be determined. Most interestingly, the kinetics of vesicle disintegration on mercury share important features with the process of vesicle fusion and, thus, sheds light also on mechanisms of endocytosis and exocytosis. Most importantly, not only artificial vesicles (liposomes) can be studied with this approach, but also reconstituted plasma membrane vesicles and even intact mitochondria. Hence, one can expect that the method may provide in future studies also information on the membrane properties of various other vesicles, including exosomes, and may allow investigating various aspects of drug action in relation to membrane properties (transmembrane transport, tissue targeting, bioavailability, etc.), and also the impact of pathophysiological conditions (e.g., oxidative modification) on membrane properties, on a hitherto not or only hardly accessible level.

  • 13.
    Agmo Hernández, Víctor
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Reijmar, Karin
    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.
    Label-Free Characterization of Peptide-Lipid Interactions Using Immobilized Lipodisks2013Ingår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 85, nr 15, s. 7377-7384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lipodisks, planar lipid bilayer structures stabilized by PEG-ylated lipids, were in the present study covalently bound and immobilized onto sensors for quartz crystal microbalance with dissipation monitoring (QCM-D) studies. It is shown that the modified sensors can be used to characterize the interaction of lipodisks with α-helical amphiphilic peptides with an accuracy similar to that obtained with well established fluorimetric approximations. The method presented has the great advantage that it can be used with peptides in their native form even if no fluorescent residues are present. The potential of the method is illustrated by determining the parameters describing the association of melittin, mastoparan X, and mastoparan with immobilized lipodisks. Both thermodynamic and kinetic analyses are possible. The presented method constitutes a useful tool for fundamental studies of peptide–membrane interactions and can also be applied to optimize the design of lipodisks, for example, for sustained release of antimicrobial peptides in therapeutic applications.

  • 14.
    Agmo Hernández, Víctor
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Samuelsson, Jörgen
    Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88 Karlstad, Sweden.
    Forssén, Patrik
    Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88 Karlstad, Sweden.
    Fornstedt, Torgny
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88 Karlstad, Sweden.
    Enhanced interpretation of adsorption data generated by liquid chromatography and by modern biosensors2013Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1317, nr SI, s. 22-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study we demonstrate the importance of proper data processing in adsorption isotherm estimations. This was done by investigating and reprocessing data from five cases on two closely related platforms: liquid chromatography (LC) and biosensors. The previously acquired adsorption data were reevaluated and reprocessed using a three-step numerical procedure: (i) preprocessing of adsorption data, (ii) adsorption data analysis and (iii) final rival model fit. For each case, we will discuss what we really measure and what additional information can be obtained by numerical processing of the data. These cases clearly demonstrate that numerical processing of LC and biosensor data can be used to gain deeper understanding of molecular interactions with adsorption media. This is important because adsorption data, especially from biosensors, is often processed using old and simplified methods.

  • 15.
    Agmo Hernández, Víctor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    The theory of metal electronucleation applied to the study of fundamental properties of liposomes2013Ingår i: Journal of Solid State Electrochemistry, ISSN 1432-8488, E-ISSN 1433-0768, Vol. 17, nr 2 (SI), s. 299-305Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    This short review describes how the theory of electrochemical metal nucleation considering non-stationary effects due to the activation of latent nucleation sites has been successfully translated and applied to describe phenomena observed on lipid membranes. This rather unexpected connection is merely formal, but has resulted in a completely new approach in liposome research. It has been proposed that hydrophobic active sites spontaneously and constantly appear and disappear on lipid membranes. These sites control the affinity of liposomes for hydrophobic surfaces and determine the permeability of the lipid membrane to small hydrophilic molecules. Thus, the kinetic models for liposome adhesion on hydrophobic substrates and for the spontaneous leakage of liposomal content are identical to that of non-stationary nucleation mentioned above. Therefore, the broad scope of the available work on metal nucleation has facilitated the interpretation of the data obtained in liposome research. Future applications of the nucleation model in the realm of liposomes are also discussed.

  • 16.
    Ahlgren, Sara
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Fondell, Amelie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. Swedish Radiat Safety Author, Res Unit, Solna Strandvag 96, SE-17116 Stockholm, Sweden.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    EGF-targeting lipodisks for specific delivery of poorly water-soluble anticancer agents to tumour cells2017Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, nr 36, s. 22178-22186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Concerns regarding poor aqueous solubility, high toxicity and lack of specificity impede the translation of many hydrophobic anticancer agents into safe and effective anticancer drugs. The application of colloidal drug delivery systems, and in particular the use of lipid-based nanocarriers, has been identified as a promising means to overcome these issues. PEG-stabilized lipid nanodisks (lipodisks) have lately emerged as a novel type of biocompatible, nontoxic and adaptable drug nanocarrier. In this study we have explored the potential of lipodisks as a platform for formulation and tumour targeted delivery of hydrophobic anticancer agents. Using curcumin as a model compound, we show that lipodisks can be loaded with substantial amounts of hydrophobic drugs (curcumin/lipid molar ratio 0.15). We demonstrate moreover that by deliberate choice of preparation protocols the lipodisks can be provided with relevant amounts of targeting proteins, such as epidermal growth factor (EGF). Data from in vitro cell studies verify that such EGF-decorated curcumin-loaded lipodisks are capable of EGF-receptor specific targeting of human A-431 tumour cells, and strongly suggest that the interaction between the lipodisks and the tumour cells results in receptor-mediated internalization of the disks and their cargo.

  • 17. Ahlgren, Sara
    et al.
    Reijmar, Karin
    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.
    EGF-targeting lipodisks for specific delivery of cationic amphiphilic peptides to tumour cellsManuskript (preprint) (Övrigt vetenskapligt)
  • 18.
    Ahlgren, Sara
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Reijmar, Karin
    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.
    Targeting lipodisks enable selective delivery of anticancer peptides to tumor cells2017Ingår i: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 13, nr 7, s. 2325-2328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Issues concerning non-specificity, degradation and hemolysis severely hamper the development of membranolytic amphiphilic peptides into safe and efficient anticancer agents. To increase the therapeutic potential, we have previously developed a strategy based on formulation of the peptides in biocompatible nanosized lipodisks. Studies using melittin as model peptide show that the proteolytic degradation and hemolytic effect of the peptide are substantially reduced upon loading in lipodisks. Here, we explored the possibilities to increase the specificity and boost the cytotoxicity of melittin to tumor cells by use of targeting lipodisk. We demonstrate that small (~20 nm) EGF-targeted lipodisks can be produced and loaded with substantial amounts of peptide (lipid/peptide molar ratio >7) by means of a simple and straightforward preparation protocol. In vitro cell studies confirm specific binding of the peptide-loaded disks to tumor cells and suggest that cellular internalization of the disks results in a significantly improved cell-killing effect.

  • 19.
    Ahmad, Shabbir
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Hysteretic Behavior, Regioselectivity, and Role of Salt Bridging Residues at the Domain Interface of Potato Epoxide Hydrolase StEH1, Site-Directed Mutagenesis and Kinetic Study2009Självständigt arbete på avancerad nivå (masterexamen), 30 poäng / 45 hpStudentuppsats (Examensarbete)
  • 20.
    Aksoy, N. H.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi. Aksaray Univ, Dept Biochem, Aksaray, Turkey..
    Mannervik, B.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Inhibitory effects of ethacrynic acid on glutathione S-transferase A1-1 from Callithrix jacchus2015Ingår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 282, s. 348-348Artikel i tidskrift (Övrigt vetenskapligt)
  • 21.
    Al-Amin, Rasel A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Science for Life Laboratory, SciLifeLab, Science for Life Laboratory, SciLifeLab.
    Johansson, Lars
    Division of Translational Medicine & Chemical Biology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet.
    Landegren, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet.
    Löf, Liza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Abdurakhmanov, Eldar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Blokzijl, Andries
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Svensson, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lönn, Peter
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Dept. Of Immunology, Genetics and Pathology,.
    Söderberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Danielson, U. Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lundbäck, Thomas
    Division of Translational Medicine & Chemical Biology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Target Engagement-Mediated Amplification for Monitoring Drug-Target Interactions in SituManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    It is important to determine the localization of drugs or drug candidates at cellular and subcellular resolution in relevant clinical specimens. This is necessary to evaluate drug candidates from early stages of drug development to clinical evaluation of mutations potentially causing resistance to targeted therapy. We describe a technology where oligonucleotide-conjugated drug molecules are used to visualize and measure target engagement in situ via rolling-circle amplification (RCA) of circularized oligonucleotide probes (padlock probes). We established this target engagement-mediated amplification (TEMA) technique using kinase inhibitor precursor compounds, and we applied the assay to investigate target interactions by microscopy in pathology tissue sections and using flow cytometry for blood samples from patients, as well as in commercial arrays including almost half of all human proteins.  In the variant proxTEMAtechnique, in situ proximity ligation assays were performed by combining drug-DNA conjugates with antibody-DNA conjugates to specifically reveal drug binding to particular on- or off-targets in pathological tissues sections. In conclusion, the TEMA methods successfully visualize drug-target interaction by experimental and clinically approved kinase inhibitors in situ and with kinases among a large collection of arrayed proteins. 

  • 22.
    Ali Ahmed, Said
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Investigation of epoxide hydrolase activity in Saccharomyces cerevisiae ORF YNR064c protein2013Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 23. Ali, M. A. E.
    et al.
    Abdel-Fatah, O. M.
    Janson, Jan-Christer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Elshafei, A. M.
    Antimicrobial potential of Saccharomyces boulardii extracts and fractions2012Ingår i: Journal of Applied Sciences Research, ISSN 1816-157X, E-ISSN 1819-544X, Vol. 8, nr 8, s. 4537-4543Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Different extracts of viable therapeutic Saccharomyces boulardii cells were evaluated for their antimicrobial activities against Escherichia coli and Candida albicans. Water, methanol, isopropanol, n-butanol and ethanol were used as solvents for extraction. Ethanol-extract exhibited the highest antimicrobial activity towards both strains, followed by water-extract. No antimicrobial activity could be detected on testing methanol-extract towards both strains. Ethanol- and water-extracts, cells remaining after water and ethanol extraction and broth were also tested for their antimicrobial activities against Gram-positive, Gram-negative, non-filamentous and filamentous fungi and showed considerable amounts of antimicrobial activities. Ethanol extracts exhibited the highest antimicrobial activity against all the tested strains, was then fractionated on a Sephadex G-100 column and the obtained fractions were examined using the agar-well diffusion method against Staphylococcus aureus, E.coli, C. albicans and Aspergillus niger. Results obtained indicate the presence of different scattered active fractions with different potencies against the four tested microorganisms. A large scale fermentation process was conducted using a BioFlo benchtop-15L Fermentor/ Bioreactor and the products were evaluated for their antimicrobial activities.

  • 24.
    Ali, Muhammad
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Ivarsson, Ylva
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    High-throughput discovery of functional disordered regions2018Ingår i: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292, Vol. 14, nr 5, artikel-id e8377Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Partially or fully intrinsically disordered proteins are widespread in eukaryotic proteomes and play important biological functions. With the recognition that well defined protein structure is not a fundamental requirement for function come novel challenges, such as assigning function to disordered regions. In their recent work, Babu and colleagues (Ravarani etal,) took on this challenge by developing IDR-Screen, a robust high-throughput approach for identifying functions of disordered regions.

  • 25.
    Almandoz-Gil, Leire
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Welander, Hedvig
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ihse, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Khoonsari, Payam Emami
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Musunuri, Sravani
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lendel, Christofer
    KTH Royal Inst Technol, Dept Chem, Stockholm, Sweden.
    Sigvardson, Jessica
    BioArctic AB, Stockholm, Sweden.
    Karlsson, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Bergström, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Corrigendum to “Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways” [Free Rad. Biol. Med. (2017) 421–431]2018Ingår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 117, s. 258-258Artikel i tidskrift (Refereegranskat)
  • 26.
    Almandoz-Gil, Leire
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Welander, Hedvig
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ihse, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Khoonsari, Payam Emami
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Musunuri, Sravani
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lendel, Christofer
    KTH, Royal Institute of Technology, Sweden.
    Sigvardson, Jessica
    BioArctic AB, Sweden.
    Karlsson, Mikael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Bergström, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways2017Ingår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 110, s. 421-431Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal inclusions found in brains with Parkinson's disease and dementia with Lewy bodies. A body of evidence implicates oxidative stress in the pathogenesis of these diseases. For example, a large excess (30:1, aldehyde:protein) of the lipid peroxidation end products 4-oxo-2-nonenal (ONE) or 4-hydroxy-2-nonenal (HNE) can induce alpha-synuclein oligomer formation. The objective of the study was to investigate the effect of these reactive aldehydes on alpha-synuclein at a lower molar excess (3:1) at both physiological (7.4) and acidic (5.4) pH. As observed by size-exclusion chromatography, ONE rapidly induced the formation of alpha-synuclein oligomers at both pH values, but the effect was less pronounced under the acidic condition. In contrast, only a small proportion of alpha-synuclein oligomers were formed with low excess HNE-treatment at physiological pH and no oligomers at all under the acidic condition. With prolonged incubation times (up to 96 h), more alpha-synuclein was oligomerized at physiological pH for both ONE and HNE. As determined by Western blot, ONE-oligomers were more SDS-stable and to a higher-degree cross-linked as compared to the HNE-induced oligomers. However, as shown by their greater sensitivity to proteinase K treatment, ONE-oligomers, exhibited a less compact structure than HNE-oligomers. As indicated by mass spectrometry, ONE modified most Lys residues, whereas HNE primarily modified the His50 residue and fewer Lys residues, albeit to a higher degree than ONE. Taken together, our data show that the aldehydes ONE and HNE can modify alpha-synuclein and induce oligomerization, even at low molar excess, but to a higher degree at physiological pH and seemingly through different pathways.

  • 27.
    Almaqwashi, Ali A.
    et al.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Andersson, Johanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Chalmers, Dept Chem & Chem Engn, S-41296 Gothenburg, Sweden..
    Lincoln, Per
    Chalmers, Dept Chem & Chem Engn, S-41296 Gothenburg, Sweden..
    Rouzina, Ioulia
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA..
    Westerlund, Fredrik
    Chalmers, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Williams, Mark C.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation2016Ingår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 110, nr 6, s. 1255-1263Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [mu-dppzip(phen)(4)Ru-2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)(2)dppz) and the distal subunit (Ru(phen)(2)ip), respectively, each of which can be either right-handed (Delta) or left-handed (Lambda). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Delta x(eq), and the dynamic DNA structural deformations during ligand association x(on) and dissociation x(off). We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a K-d of 27 +/- 3 nM for (Delta,Lambda)-Piz to a K-d of 622 +/- 55 nM for (Lambda,Delta)-Piz. The striking affinity decrease is correlated with increasing Delta x(eq) from 0.30 +/- 0.02 to 0.48 +/- 0.02 nm and x(on) from 0.25 +/- 0.01 to 0.46 +/- 0.02 nm, but limited x(off) changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics.

  • 28.
    Almaqwashi, Ali A.
    et al.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA.;King Abdulaziz Univ, Dept Phys, Rabigh 21911, Saudi Arabia..
    Andersson, Johanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Chalmers, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden..
    Lincoln, Per
    Chalmers, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden..
    Rouzina, Ioulia
    Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA..
    Westerlund, Fredrik
    Chalmers, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden..
    Williams, Mark C.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    DNA intercalation optimized by two-step molecular lock mechanism2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 37993Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The diverse properties of DNA intercalators, varying in affinity and kinetics over several orders of magnitude, provide a wide range of applications for DNA-ligand assemblies. Unconventional intercalation mechanisms may exhibit high affinity and slow kinetics, properties desired for potential therapeutics. We used single-molecule force spectroscopy to probe the free energy landscape for an unconventional intercalator that binds DNA through a novel two-step mechanism in which the intermediate and final states bind DNA through the same mono-intercalating moiety. During this process, DNA undergoes significant structural rearrangements, first lengthening before relaxing to a shorter DNA-ligand complex in the intermediate state to form a molecular lock. To reach the final bound state, the molecular length must increase again as the ligand threads between disrupted DNA base pairs. This unusual binding mechanism results in an unprecedented optimized combination of high DNA binding affinity and slow kinetics, suggesting a new paradigm for rational design of DNA intercalators.

  • 29.
    Almaqwashi, Ali A.
    et al.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Andersson, Johanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden..
    Lincoln, Per
    Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden..
    Rouzina, Ioulia
    Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA..
    Westerlund, Fredrik
    Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden..
    Williams, Mark C.
    Northeastern Univ, Dept Phys, Boston, MA 02115 USA..
    Resolving the DNA Binding Mode of a Rotationally Flexible Binuclear Ruthenium Complex2015Ingår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, nr 2, s. 396A-396AArtikel i tidskrift (Övrigt vetenskapligt)
  • 30.
    Almokhtar, Mokhtar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Wikvall, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Ubhayasekera, S. J. Kumari A.
    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.
    Norlin, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Motor neuron-like NSC-34 cells as a new model for the study of vitamin D metabolism in the brain.2016Ingår i: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 158, s. 178-188Artikel i tidskrift (Refereegranskat)