title: Weak affinity chromatography for evaluation of stereoisomers in early drug discovery.
abstract: In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.
authors.affiliation: School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
authors.forename: Minh-Dao
authors.initials: MD
authors.lastname: Duong-Thi
authors.forename: Maria
authors.initials: M
authors.lastname: Bergström
authors.forename: Tomas
authors.initials: T
authors.lastname: Fex
authors.forename: Susanne
authors.initials: S
authors.lastname: Svensson
authors.forename: Sten
authors.initials: S
authors.lastname: Ohlson
authors.forename: Roland
authors.initials: R
authors.lastname: Isaksson
mesh_terms: D002846:Chromatography, Affinity / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013237:Stereoisomerism; D013917:Thrombin / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D013917:Thrombin
keywords: fragment-based drug discovery; mixture screening; stereoisomers; thrombin; weak affinity chromatography