title: Calpain inhibitors based on the quiescent affinity label concept: high rates of calpain inactivation with leaving groups derived from N-hydroxy peptide coupling reagents.
abstract: A series of irreversible inhibitors of recombinant calpain has been synthesized and their rates of inactivation have been evaluated against calpain and cathepsin B, respectively. The design of the inhibitors was based on the quiescent affinity label concept. By choosing the appropriate affinity group and by employing leaving groups derived from N-hydroxy coupling reagents, good inhibitors of calpain with high rates of inactivation have been identified. However, poor aqueous stability limits their therapeutic utility.
authors.affiliation: Cephalon, Inc., West Chester, PA 19380, USA. rtripath@cephalon.com
authors.forename: R
authors.initials: R
authors.lastname: Tripathy
authors.forename: M A
authors.initials: MA
authors.lastname: Ator
authors.forename: J P
authors.initials: JP
authors.lastname: Mallamo
mesh_terms: D000345:Affinity Labels / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors*; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007202:Indicators and Reagents; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000345:Affinity Labels; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D007202:Indicators and Reagents; D009842:Oligopeptides; D011994:Recombinant Proteins; D002154:Calpain; D002401:Cathepsin B