title: 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.
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Litovchick
authors.affiliation: Novartis Pharma AG, Institutes of Biomedical Research, Basel, Switzerland.
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Dumelin
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Sevan
authors.initials: S
authors.lastname: Habeshian
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Gikunju
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Guié
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Centrella
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Sigel
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Cuozzo
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Keefe
authors.affiliation: X-Chem Pharmaceuticals, 100 Beaver St., Waltham, MA, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Clark
mesh_terms: D055808:Drug Discovery / Q000379:methods; D015723:Gene Library; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D054852:Small Molecule Libraries
chemical_list: D009841:Oligonucleotides; D054852:Small Molecule Libraries