Small-molecule inhibitor: arphamenine A

Name

History: The arphamenines were first described by Umezawa and co-workers (Umezawa et al., 1983) as products of Chromobacterium violaceum strain BMG361-CF4.
Peptidases inhibited: Arphamenines A and B are selective inhibitors of aminopeptidase B (Ohuchi et al., 1984). Leukotriene A4 hydrolase is inhibited much more weakly, with micromolar K_i (Orning et al., 1994).
Mechanism: Arphamenines A and B are ketomethylene analogues of the dipeptides Arg-Phe and Arg-Tyr, respectively. They cause reversible inhibition by acting as transition state analogues of the N-terminal arginine residues that are the substrates of the affected peptidases (Harbeson & Rich, 1988).

CID at PubChem: 128774
Structure
Chemical/biochemical name: 5-amino-2-benzyl-8-guanidino-4-oxo-octanoic acid hydrochloride
Formula weight: 357
Related inhibitors: Analogous ketomethylene pseudodipeptides (Garcia-Lopez et al.,1992)

Inhibitor class: This compound is of the ketomethylene class of peptidase inhibitors, in which the would-be scissile peptide bond, -CO.NH-, is replaced by a ketomethylene group, -CO.CH₂- (Almquist et al., 1980). The ketomethylene linkage is not hydrolysable by a peptidase, but may be tightly bound as an analogue of the transition state intermediate (Harbeson & Rich, 1989). Reviewed by Powers & Harper (1986).