Small-molecule inhibitor: Z-Phe-Arg-diazomethane

Name

History: The synthesis of Z-Phe-Arg-diazomethane and its characterization as a peptidase inhibitor were described by Zumbrunn et al. (1988).
Peptidases inhibited: Z-Phe-Arg-diazomethane is a particularly effective inhibitor of clostripain, but it also inhibits cathepsin B (Zumbrunn et al., 1988).
Mechanism: Clostripain is irreversibly inhibited (second-order rate constant 86000 M^-1s^-1).

Structure
Chemical/biochemical name: benzyloxycarbonyl-phenylalanyl-arginyldiazomethane

Inhibitor class: This is a compound of the peptidyl-diazomethane class of cysteine peptidase inhibitors. Peptidyl-diazomethanes (or -diazomethyl ketones) were described by Green & Shaw (1981) as specific inactivators of cysteine peptidases. With a suitable peptide component to direct specificity, effective inhibitors have been developed for a number of cysteine peptidases. Under some conditions peptidases of other catalytic classes may be inhibited, however, although usually at much lower rates. Such exceptions include plasma kallikrein: Zumbrunn et al., 1988), prolyl oligopeptidase: Stone et al., 1992), oligopeptidase B: Kornblatt et al., 1992), some subtilisins (family S8: Ermer et al., 1990) and a proteasome component: Reidlinger et al., 1997). The peptidyl-diazomethane inhibitors of cysteine peptidases have been reviewed by Powers et al. (2002), pp. 4656 - 4657.
Reviews: Powers et al. (2002), pp. 4656 - 4657.