从3.34亿DNA编码化合物库中发现sEH抑制剂.pdfVIP

/scientificreports OPEN Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a Received: 15 January 2015 Accepted: 21 April 2015 334-Million Member Library Published: 10 June 2015 1 2 1 1 Alexander Litovchick , Christoph E. Dumelin , Sevan Habeshian , Diana Gikunju , 1 1 1 1 1 Marie-Aude Guié , Paolo Centrella , Ying Zhang , Eric A. Sigel , John W. Cuozzo , 1 1 Anthony D. Keefe Matthew A. Clark 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. In the past decade, DNA-encoding of small molecule libraries has emerged as an