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Enzyme Isoselective Inhibitors: Application to Drug Design
Author(s) -
Shokhen Michael,
Khazanov Netaly,
Albeck Am
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200600030
Subject(s) - enzyme , binding affinities , affinities , chemistry , rational design , computational biology , stereochemistry , combinatorial chemistry , drug design , ligand (biochemistry) , serine , cysteine , drug , biochemistry , biology , nanotechnology , pharmacology , materials science , receptor
Common methodologies of computer‐assisted drug design focus on noncovalent enzyme–ligand interactions. We introduced enzyme isoselective inhibition trend analysis as a tool for the expert analysis of covalent reversible inhibitors. The methodology is applied to predict the binding affinities of a series of transition‐state analogue inhibitors of medicinally important serine and cysteine hydrolases. These inhibitors are isoselective: they have identical noncovalent recognition fragments ( RS ) and different reactive chemical fragments ( CS ). Furthermore, it is possible to predict the binding affinities of a series of isoselective inhibitors toward a prototype enzyme and to extrapolate the data to a target medicinally important enzyme of the same family. Rational design of CS fragments followed by conventional RS optimization could be used as a novel approach to drug design.