TY - DATA T1 - A Fragment-Based Approach to Identifying S‑Adenosyl‑l‑methionine -Competitive Inhibitors of Catechol O‑Methyl Transferase (COMT). PY - 2014/06/26 AU - Marion Lanier AU - Geza Ambrus AU - Derek C. Cole AU - Richard Davenport AU - Jonathan Ellery AU - Richard Fosbeary AU - Andy J. Jennings AU - Akito Kadotani AU - Yusuke Kamada AU - Ruhi Kamran AU - Shin-Ichi Matsumoto AU - Atsushi Mizukami AU - Shoichi Okubo AU - Kengo Okada AU - Kumar Saikatendu AU - Louise Walsh AU - Haihong Wu AU - Mark S. Hixon UR - https://acs.figshare.com/articles/dataset/A_Fragment_Based_Approach_to_Identifying_i_S_i_Adenosyl_l_methionine_Competitive_Inhibitors_of_Catechol_i_O_i_Methyl_Transferase_COMT_/2279371 DO - 10.1021/jm500475k.s003 L4 - https://ndownloader.figshare.com/files/3915712 KW - LE KW - transferase KW - Competitive Inhibitors KW - SAM binding pocket KW - bisaryl fragments KW - COMT inhibitors N2 - 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. ER -