title: Peptidyl allyl sulfones: a new class of inhibitors for clan CA cysteine proteases.
abstract: A new series of peptidyl allyl sulfone inhibitors was discovered while trying to synthesize epoxy sulfone inhibitors from vinyl sulfones using basic oxidizing conditions. The various dipeptidyl allyl sulfones were evaluated with calpain I, papain, cathepsins B and L, cruzain and rhodesain and found to be potent inhibitors. In comparison to the previously developed class of vinyl sulfone inhibitors, the novel dipeptidyl allyl sulfones were more potent inhibitors than the corresponding dipeptidyl vinyl sulfones. It was observed that the stereochemistry of the vinyl sulfone precursor played a role in the potency of the dipeptidyl allyl sulfone inhibitor.
authors.affiliation: School of Chemistry and Biochemistry and the Petit Institute of Bioscience and Bioengineering, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
authors.forename: Marion G
authors.initials: MG
authors.lastname: Götz
authors.forename: Conor R
authors.initials: CR
authors.lastname: Caffrey
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hansell
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
authors.forename: James C
authors.initials: JC
authors.lastname: Powers
mesh_terms: D000818:Animals; D002417:Cattle; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D013450:Sulfones; C009873:divinyl sulfone; D003546:Cysteine Endopeptidases