Additional Peptidyl Diazomethyl Ketones, Including Biotinyl Derivatives, Which Affinity-Label Calpain and Related Cysteinyl Proteinases

Abstract

Calpain, the calcium-activated cysteinyl proteinase, can be irreversibly inactivated by peptidyl diazomethyl ketones in which the peptide portion contains a penultimate leucine residue. Some new derivatives of this type have been synthesized and examined for their rates of inactivation of chicken gizzard and human platelet calpain. Two derivatives containing a C-terminal biotin residue, Biot-Aca-Leu-TyrCHN₂ and Biot-Aca-Leu-Leu-TyrCHN₂, have also been prepared in the expectation that their application to the study of the function of calpain and related proteases will prove fruitful.

Key Words: :

• Calpain
• cysteinyl proteases
• inhibitors
• peptidyl diazomethyl ketones