Alexander Litovchick; Christoph E. Dumelin; Sevan Habeshian; Diana Gikunju; Marie-Aude Guié; Paolo A. Centrella; Ying Zhang; Eric A. Sigel; John W. Cuozzo; Anthony D. Keefe; Matthew A. Clark
Sci. Rep., 2015, 5, 10916
https://doi.org/10.1038/srep10916

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.