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Rapid screening of enzymes for the enzymatic hydrolysis of chiral esters in drug discovery
Author(s) -
Petucci Chris,
Di Li,
McConnell Oliver
Publication year - 2007
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20432
Subject(s) - chemistry , enzyme , enzymatic hydrolysis , drug discovery , hydrolysis , chromatography , organic chemistry , combinatorial chemistry , biochemistry
Thirty‐five enzymes were rapidly screened for their ability to selectively hydrolyze chiral esters to their corresponding carboxylic acids for the efficient generation of chiral intermediates in drug discovery. Optimization of the enzymatic reactions at various incubation times was performed using a robotic liquid handler. Enantiomeric pairs of chiral esters and carboxylic acids were then analyzed simultaneously by chiral GC/MS in a single analysis. This analytical approach is particularly useful for compounds that do not possess a conjugated chromophore or are volatile and difficult to analyze by chiral HPLC/UV or HPLC/MS. The resulting data was used to determine enantiomeric excesses and percent conversions to the desired enantiomer of the carboxylic acid for the selection of efficient enzymes for bioconversions in drug discovery in a pharmaceutical company. Chirality, 2007. © 2007 Wiley‐Liss, Inc.