Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins. 2016

Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
Linnaeus University, Department of Chemistry and Biomedical Sciences, SE-39182 Kalmar, Sweden.

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.

UI MeSH Term Description Entries
D008051 Lipid Bilayers Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D002846 Chromatography, Affinity A chromatographic technique that utilizes the ability of biological molecules, often ANTIBODIES, to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Bioaffinity,Immunochromatography,Affinity Chromatography,Bioaffinity Chromatography
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012822 Silicon Dioxide Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, QUARTZ, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. Silica,Aerosil,Aerosil 380,Cristobalite,Quso G-32,Quso G32,Tridymite,380, Aerosil,Dioxide, Silicon,G32, Quso,Quso G 32
D016062 Porosity Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. Porosities
D051398 Aquaporin 1 Aquaporin 1 forms a water-specific channel that is constitutively expressed at the PLASMA MEMBRANE of ERYTHROCYTES and KIDNEY TUBULES, PROXIMAL. It provides these cells with a high permeability to WATER. In humans polymorphisms of this protein result in the Colton blood group antigen. AQP-CHIP Protein,AQP1 Protein,Aquaporin 1 Protein,Aquaporin-CHIP,CHIP28 Protein,Channel-Forming Integral Membrane Protein Of 28 kDa,AQP CHIP Protein,Aquaporin CHIP,Channel Forming Integral Membrane Protein Of 28 kDa

Related Publications

Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
November 2019, Expert opinion on drug discovery,
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
July 2013, Analytical chemistry,
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
November 2012, Analytical and bioanalytical chemistry,
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
August 2018, Methods (San Diego, Calif.),
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
October 2023, Molecules (Basel, Switzerland),
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
April 2006, Structure (London, England : 1993),
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
July 1987, Journal of chromatography,
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
January 2000, Methods in molecular biology (Clifton, N.J.),
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
January 2021, Methods in molecular biology (Clifton, N.J.),
Minh-Dao Duong-Thi, and Maria Bergström, and Katarina Edwards, and Jonny Eriksson, and Sten Ohlson, and Janet To Yiu Ying, and Jaume Torres, and Víctor Agmo Hernández
January 2024, Biochemistry,
Copied contents to your clipboard!