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Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Nanyang Technol University, Singapore.
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
Uppsala University.
Uppsala University.
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2016 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, no 3, p. 981-988Article in journal (Refereed) Published
Abstract [en]

Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures.

Place, publisher, year, edition, pages
2016. Vol. 141, no 3, p. 981-988
National Category
Analytical Chemistry
Research subject
Chemistry, Analytical Chemistry
Identifiers
URN: urn:nbn:se:lnu:diva-50634DOI: 10.1039/c5an02105gISI: 000368942600028PubMedID: 26673836Scopus ID: 2-s2.0-84956759926OAI: oai:DiVA.org:lnu-50634DiVA, id: diva2:911468
Available from: 2016-03-11 Created: 2016-03-11 Last updated: 2017-11-30Bibliographically approved

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Duong-Thi, Minh-DaoBergström, MariaOhlson, Sten

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CiteExportLink to record
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Citation style
  • apa
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