Small-molecule inhibitor: poststatin

Name

History: Poststatin is a natural product of Streptomyces viridochromogenes first described by Aoyagi et al. (1991).
Peptidases inhibited: Prolyl oligopeptidase.
Mechanism: Inhibition is reversible, being mediated primarily by the alpha-keto group of the 3-amino-2-oxovaleryl moiety (Nagai et al., 1991).
Pharmaceutical relevance: Prolyl oligopeptidase is regarded as a potential drug target for certain neuropathologies, and several inhibitors have been shown to be pharmacologically active.

Structure
Chemical/biochemical name: L-valyl-L-valyl-3-amino-2-oxovaleryl-D-leucyl-L-valine

Comment: Compounds related to poststatin that are more potent inhibitors of prolyl oligopeptidase include benzyloxycarbonyl-L-homophenylalanyl-(RS)-3-amino-2-oxovaleryl-D-leucyl-L-valine (Tsuda et al., 1996) and benzyloxycarbonyl-L-phenylalanyl-(S)-2-oxo-2-(2-pyrrolidinyl)acetyl-D-phenylalanine (Tsuda et al., 1996).