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Repurposing Suzuki Coupling Reagents as a Directed Fragment Library Targeting Serine Hydrolases and Related Enzymes.

ABSTRACT: Serine hydrolases are susceptible to potent reversible inhibition by boronic acids. Large collections of chemically diverse boronic acid fragments are commercially available because of their utility in coupling chemistry. We repurposed the approximately 650 boronic acid reagents in our collection as a directed fragment library targeting serine hydrolases and related enzymes. Highly efficient hits (LE > 0.6) often result. The utility of the approach is illustrated with the results against autotaxin, a phospholipase implicated in cardiovascular disease.

SUBMITTER: Lanier M

PROVIDER: S-EPMC5483892 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Repurposing Suzuki Coupling Reagents as a Directed Fragment Library Targeting Serine Hydrolases and Related Enzymes.

Lanier Marion M Cole Derek C DC Istratiy Yelena Y Klein Michael G MG Schwartz Phillip A PA Tjhen Richard R Jennings Andy A Hixon Mark S MS

Journal of medicinal chemistry 20170609 12

Serine hydrolases are susceptible to potent reversible inhibition by boronic acids. Large collections of chemically diverse boronic acid fragments are commercially available because of their utility in coupling chemistry. We repurposed the approximately 650 boronic acid reagents in our collection as a directed fragment library targeting serine hydrolases and related enzymes. Highly efficient hits (LE > 0.6) often result. The utility of the approach is illustrated with the results against autotax ...[more]

PMID: 28564542

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