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Bisubstrate Inhibitors of the Enzyme Catechol O ‐Methyltransferase (COMT): Efficient Inhibition Despite the Lack of a Nitro Group
Author(s) -
Paulini Ralph,
Lerner Christian,
JakobRoetne Roland,
Zürcher Gerhard,
Borroni Edilio,
Diederich François
Publication year - 2004
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400084
Subject(s) - nitro , catechol o methyl transferase , chemistry , enzyme , methyltransferase , catechol , enzyme inhibition , stereochemistry , group (periodic table) , biochemistry , combinatorial chemistry , organic chemistry , methylation , allele , alkyl , gene
A new generation of bisubstrate inhibitors for the S ‐adenosylmethionine‐ and magnesium ion‐dependent enzyme catechol O ‐methyltransferase (COMT), feature binding affinities (IC 50 values) in the double‐digit nanomolar range despite the lack of a nitro group on the catechol moiety. Inhibitor potency does not directly correlate with the p K a value of the catechol HO groups and is strongly enhanced by hydrophobic aromatic substituents attached in a biaryl‐type fashion to position 5 of the catechol ring.