Small-molecule inhibitor: iodoacetate

Name

History: Iodoacetate has long been known as an irreversible inhibitor of papain and other cysteine peptidases (e.g. Wallenfels & Eisele, 1968).
Peptidases inhibited: Cysteine peptidases are inhibited. Half-times (s) for inhibition at 10 micromolar inhibitor (Salvesen & Nagase, 2001) are: 30 (papain), 156 (cathepsin B), 592 (cathepsin H). The inhibition of glycyl endopeptidase) is extremely slow (Buttle et al., 1990).
Mechanism: Inhibition is irreversible, via alkylation of the catalytic thiol group, but it is notable that the reaction of iodoacetate with papain is faster than that of iodoacetamide, as a result of ionic interactions in the active site (Wallenfels & Eisele, 1968; Halasz & Polgar, 1977). This difference is observed with other peptidases in family C1, but not with cysteine peptidases in other families, such as legumain (Csoma & Polgar, 1984), clostripain (Kembhavi et al., 1991) and rhinovirus picornain 2A (Sarkany et al., 2000).