title: Toward high-throughput drug screening on a chip-based parallel affinity separation platform.
abstract: High-throughput screening of compound libraries, including the study of fragments, has become one of the cornerstones in modern drug discovery research. During this process hits are defined that may be developed into valuable leads and eventually into possible drug candidates. In this paper, we have demonstrated that parallel zonal weak affinity chromatography in microcolumns on a chip offers a possible screening format for weakly binding ligands toward a protein target. We used albumin as a model system because this transport protein is well established as a binder (both weak and strong) for drug substances. Bovine serum albumin was immobilized on microparticulate diolsilica particles and then packed into a 24-channel cartridge, which served as the separation platform. Analysis of the obtained chromatograms yielded information about affinity even in the millimolar range. Employing this approach, thousands of substances can be screened in just a day. We feel confident that zonal affinity chromatography will provide a useful technology in the future for performing high-throughput screening.
authors: School of Natural Sciences, Linnaeus University, Kalmar, Sweden. sten.ohlson@lnu.se
authors: Sten
authors: S
authors: Ohlson
authors: Minh-Dao
authors: MD
authors: Duong-Thi
authors: Maria
authors: M
authors: Bergström
authors: Tomas
authors: T
authors: Fex
authors: Lennart
authors: L
authors: Hansson
authors: Lennart
authors: L
authors: Pedersen
authors: Sergio
authors: S
authors: Guazotti
authors: Roland
authors: R
authors: Isaksson
mesh_terms: D000818:Animals; D002417:Cattle; D002846:Chromatography, Affinity / Q000295:instrumentation / Q000379:methods; D055808:Drug Discovery / Q000295:instrumentation / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods; D004364:Pharmaceutical Preparations / Q000032:analysis*
chemical_list: D004364:Pharmaceutical Preparations