Small-molecule inhibitor: JA-2

Summary Literature

Name

Common name: JA-2

Inhibition

History: JA-2 was desgned as an analogue of Cpp-Ala-Ala-Phe-pAb that was be more stable under biological condiditions (Shrimpton et al., 2000).
Peptidases inhibited: Thimet oligopeptidase (K_i = 23 nM) and neurolysin (K_i about 600 nM) (Steer et al., 2002).
Mechanism: Inhibition is reversible.

Chemistry

Structure
Chemical/biochemical name: N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (where Aib is alpha-amino isobutyrate)

Properties

Synthesis: Shrimpton et al. (2000)

General

Inhibitor class: This is a compound in the carboxylate class of reversible metallopeptidase inhibitors. In these, the active site zinc of the enzyme is generally coordinated by a carboxylate of the inhibitor, and this interaction contributes to inhibitory potency. Reviewed by Patchett & Cordes (1985) and Powers & Harper (1986), pp. 268 - 277 (who provide a table of K_i values).