Small-molecule inhibitor: iodoacetamide

Name

Peptidases inhibited: Iodoacetamide a general thiol-alkylating reagent, so it is expected to inhibit all cysteine peptidases, and indeed most thiol-dependent enzymes.
Mechanism: Inhibition is irreversible, by alkylation of an essential cysteine sidechain. Contrary to what might be expected simply on the basis of chemical reactivity, iodoacetamide reacts less rapidly with many cysteine peptidases than does iodoacetate at the usual pH values. The reason for the greater reactivity of iodoacetate with cysteine peptidases such as papain is apparently a favourable interaction between the positive imidazolium ion of the catalytic dyad and the negatively-charged carboxylate of the alkylating reagent (Polgar, 2004).