Weak Affinity Chromatography for Evaluation of Stereoisomers in Early Drug Discovery
Artikel i vetenskaplig tidskrift, 2013

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.

fragment-based drug discovery

weak affinity chromatography

mixture screening

thrombin

stereoisomers

Författare

M. D. Duong-Thi

Linnaeus University, Kalmar

M. Bergstrom

Linnaeus University, Kalmar

T. Fex

AstraZeneca Sweden

Susanna Eriksson

Chalmers, Kemi- och bioteknik, Skogsindustriell kemiteknik

S. Ohlson

Nanyang Technological University

Linnaeus University, Kalmar

R. Isaksson

Linnaeus University, Kalmar

Journal of Biomolecular Screening

1087-0571 (ISSN)

Vol. 18 748-755

Ämneskategorier

Kemiteknik

DOI

10.1177/1087057113480391