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

Litovchick, Alexander and Dumelin, Christoph and Habeshian, Sevan and Gikunju, Diana and Guié, Marie-Aude and Centrella, Paolo and Zhang, Ying and Sigel, Eric and Cuozzo, John and Keefe, Anthony and Clark, Matthew (2015) Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library. Scientific Reports , 5. ISSN 2045-2322

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 T4 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.

Item Type: Article
Date Deposited: 25 Apr 2016 23:45
Last Modified: 04 Jul 2016 23:45
URI: https://oak.novartis.com/id/eprint/24580

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