title: Inactivation of calpain by peptidyl fluoromethyl ketones.
abstract: The syntheses of Z-Leu-Leu-Tyr-CH2F (1) and Z-Tyr-Ala-CH2F (3) are described. The ability of Z-Leu-Leu-Tyr-CH2F (1) and Z-Leu-Tyr-CH2F (2) to inactivate in vitro calcium-activated proteinase from chicken gizzard are compared. Like the analogous diazomethyl ketones 4 and 5, these inhibitors were also found to inactivate cathepsin L in common with other inhibitors under current investigation. However, other specific inactivators for cathepsin L are available, for example, the fluoromethyl ketone 3 and diazomethyl ketone 6 of Z-Tyr-Ala-OH, which have no effect on the calcium-activated proteinase and therefore provide control inhibitors for observations made with Z-Leu-Leu-Tyr-CH2F (1).
authors.affiliation: Friedrich Miescher-Institut, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Angliker
authors.forename: J
authors.initials: J
authors.lastname: Anagli
authors.forename: E
authors.initials: E
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002645:Chickens; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D066298:In Vitro Techniques; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
chemical_list: D007659:Ketones; D009842:Oligopeptides; D002403:Cathepsins; D010450:Endopeptidases; D002154:Calpain; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534280:Ctsl protein, rat