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Updated: Apr 29, 2026

Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry CCMS
Published on: December 20, 2010
A fragment-based approach to identifying S-adenosyl-l-methionine -competitive inhibitors of catechol O-methyl
Marion Lanier1, Geza Ambrus, Derek C Cole
1Medicinal Chemistry, ‡Structural Biology, §Discovery Biology, ∥Analytical Chemistry, Takeda California Inc. , 10410 Science Center Drive San Diego California 92121, United States.
Abstract:
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.
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