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

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.

SUBMITTER: Litovchick A

PROVIDER: S-EPMC4603778 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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

Litovchick Alexander A Dumelin Christoph E CE Habeshian Sevan S Gikunju Diana D Guié Marie-Aude MA Centrella Paolo P Zhang Ying Y Sigel Eric A EA Cuozzo John W JW Keefe Anthony D AD Clark Matthew A MA

Scientific reports 20150610

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 ...[more]

PMID: 26061191

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