Small-molecule inhibitor: GEMSA

Name

History: GEMSA was described as an inhibitor of carboxypeptidase B by McKay & Plummer (1978).
Peptidases inhibited: GEMSA is a selective inhibitor of the metallocarboxypeptidases with carboxypeptidase B-like specificity. Song & Fricker (1995) report that metallocarboxypeptidase D is much more strongly inhibited than is carboxypeptidase E, for which K_i = 9 nM (Fricker et al., 1983). Also inhibited are carboxypeptidase N (K_i = 1.5 x10^-6 M: Fricker et al., 1983), carboxypeptidase M (IC₅₀ = 60 nM: Song & Fricker, 1995), carboxypeptidase B (K_i = 4x10^-6 M: McKay & Plummer, 1978), carboxypeptidase Z (IC₅₀ = 10x10^-6 M: Novikova & Fricker, 1999) and carboxypeptidase U (K_i = 18x10^-6 M: Boffa et al., 1998). Carboxypeptidase A is not significantly inhibited (McKay & Plummer, 1978).
Mechanism: Inhibition is reversible. The crystal structure of GEMSA in complex with metallocarboxypeptidase D peptidase unit 2 has been described by Aloy et al. (2001).
Pharmaceutical relevance: Tritium-labelled GEMSA has been used in a number of studies to localise metallocarboxypeptidases (e.g. Lynch et al., 1984).

CID at PubChem: 3464
Structure
Chemical/biochemical name: 2-[2-(diaminomethylideneamino)ethylsulfanyl]butanedioic acid
Formula weight: 235

Inhibitor class: This compound is a thiol-containing metallopeptidase inhibitor. In these, an interaction between the thiol group of the inhibitor and zinc in the active site of the enzyme contributes to inhibitory potency. Among the first of such compounds to be described was captopril (Cushman et al., 1977). Reviewed by Powers & Harper (1986), pp. 254 - 263. Thiol-containing metallopeptidase inhibitors include captopril, CGS 35601, GEMSA, omapatrilat, RB 101(S), thiorphan.