New path to enzyme inhibitor design

Abstract

Affinity in which a peptide moiety transports an aryl carboxylate leaving group that is uniquely reactive toward the active site of a target enzyme offer a powerful new strategy for the design of enzyme inhibitors. Enzyme inhibitors based on such affinity labels could lead to the development of new pharmaceuticals, says Allen Krantz, director of research for Syntex Research, Mississauga, Ontario. Krantz described research on the design of mechanism-based enzyme inhibitors whose reactions are mediated by the formation of acyl enzymes to a symposium sponsored by the Biotechnology Secretariat. Krantz described efforts to develop inhibitors of the enzyme cathepsin B, a cysteine protease that, in addition to its normal functions, has been implicated in a number of pathological conditions. A cathepsin  inhibitor that goes by the name 'EST is in clinical trials in Japan for the treatment of muscular dystrophy. The idea behind quiescent affinity is to take advantage of the ...