Encoded Library Synthesis Using Chemical Ligation and the Discovery of SEH Inhibitors from a 334-Million Member Library

Overview

Journal Sci Rep

Specialty Science

Date 2015 Jun 11

PMID 26061191

Citations 36

Authors

Alexander Litovchick

Christoph E Dumelin

Sevan Habeshian

Diana Gikunju

Marie-Aude Guie

Paolo Centrella

Ying Zhang

Eric A Sigel

John W Cuozzo

Anthony D Keefe

Matthew A Clark

Affiliations

Soon will be listed here.

Abstract

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.

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