American Chemical Society
Browse

sorry, we can't preview this file

jm500475k_si_003.cif (1.13 MB)

A Fragment-Based Approach to Identifying S‑Adenosyl‑l‑methionine -Competitive Inhibitors of Catechol O‑Methyl Transferase (COMT).

Download (1.13 MB)
dataset
posted on 2014-06-26, 00:00 authored by Marion Lanier, Geza Ambrus, Derek C. Cole, Richard Davenport, Jonathan Ellery, Richard Fosbeary, Andy J. Jennings, Akito Kadotani, Yusuke Kamada, Ruhi Kamran, Shin-Ichi Matsumoto, Atsushi Mizukami, Shoichi Okubo, Kengo Okada, Kumar Saikatendu, Louise Walsh, Haihong Wu, Mark S. Hixon
Catechol O-methyl transferase belongs to the diverse family of S-adenosyl-l-methionine transferases. It is a target involved in the treatment of Parkinson’s disease. Here we present a fragment-based screening approach to discover noncatechol derived COMT inhibitors which bind at the SAM binding pocket. We describe the identification and characterization of a series of highly ligand efficient SAM competitive bisaryl fragments (LE = 0.33–0.58). We also present the first SAM-competitive small-molecule COMT co-complex crystal structure.

History