Small-molecule inhibitor: antipain

Name

History: Antipain was discovered by Suda et al. (1972) in cultures of Streptomyces michigaensis and S. yokosukaensis. The structure was reported by Umezawa et al. (1972).
Peptidases inhibited: Antipain has broad inhibitory specificity, peptidases affected including papain, trypsin, thrombin, serine carboxypeptidae A, cathepsin B, plasmin and acrosin (Umezawa & Aoyagi, 1977) as well as cerevisin (Kominami et al., 1981). Reported to inactivate reversibly tyrosine hydroxylase (Okuno et al., 1987).
Mechanism: Inhibition is reversible.

CID at PubChem: 37817
Structure
Chemical/biochemical name: [(S)-1-carboxy-2-phenylethyl]-carbamoyl-L-arginyl-L-valyl-argininal
Formula weight: 605
Related inhibitors: Phenylalanyl-ureido-citrullinyl-valinyl-cycloarginal, inhibitor of gingipain R (C25.001) (Kadowaki et al., 2003). KF77-AG6 (Fujimoto et al., 1974).

Inhibitor class: This is a compound of the aldehyde class. The discovery of leupeptin in the late 1960s drew attention to the potential of aldehydes as peptidase inhibitors, and the inhibition of papain by synthetic aldehydes was further studied by Wolfenden and co-workers (e.g. Westerik & Wolfenden, 1972). Many aldehydes are now known as inhibitors of serine, cysteine or threonine peptidases. They form hemiacetal or thiohemiacetal conjugates with the essential hydroxyl or thiol group of the enzyme that are transition state analogues (Bendall et al., 1977). The compounds exist predominantly in their hydrated forms in aqueous solution, but only the aldehyde is an effective inhibitor (Bendall et al., 1977). Peptide aldehydes and semicarbazones are valuable ligands for affinity chromatography of serine and cysteine peptidases (Rich et al., 1986; Dando & Barrett, 1992). Aldehydes can also act as inhibitors of metallopeptidases (Strater & Lipscomb, 1995).
Comment: The 1-carboxy-2-phenylethyl]-carbamoyl group is present also in chymostatin.
Reviews: Umezawa & Aoyagi (1977)