The Bsmoc group as a novel scaffold for the design of irreversible inhibitors of cysteine proteases.
Carbamate and ester derivatives of the 1,1-dioxobenzo[b]thiophen-2-ylmethyloxycarbonyl (Bsmoc) scaffold react readily with thiols via a Michael addition at rates not significantly affected by the nature of the carboxylic or carbamic acid leaving group. These Michael acceptors are irreversible inhibitors of the cysteine proteases papain and human liver cathepsin B, displaying first-order kinetics with respect to inhibitor concentration. In contrast, none of the Bsmoc derivatives inhibited porcine pancreatic elastase, a serine protease.
Iley
Jim
J
Chemistry Department, The Open University, Milton Keynes, MK7 6AA, UK. j.n.iley@open.ac.uk
Moreira
Rui
R
Martins
Luísa
L
Guedes
Rita C
RC
Soares
Cláudio M
CM
D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular
D015853:Cysteine Proteinase Inhibitors