title: The Bsmoc group as a novel scaffold for the design of irreversible inhibitors of cysteine proteases.
abstract: 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.
authors.affiliation: Chemistry Department, The Open University, Milton Keynes, MK7 6AA, UK. j.n.iley@open.ac.uk
authors.forename: Jim
authors.initials: J
authors.lastname: Iley
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
authors.forename: Luísa
authors.initials: L
authors.lastname: Martins
authors.forename: Rita C
authors.initials: RC
authors.lastname: Guedes
authors.forename: Cláudio M
authors.initials: CM
authors.lastname: Soares
mesh_terms: D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular
chemical_list: D015853:Cysteine Proteinase Inhibitors