Poststatin, a New Inhibitor of Prolyl Endopeptidase

V. Endopeptidase Inhibitory Activity of Poststatin Analogues

抄録

Thirty analogues of poststatin were synthesized, and their inhibitory activities against prolyl endopeptidase, human leukocyte elastase and cathepsin B were measured. The α-ketone was essential and the S configuration was preferable to the R configuration in the β-substituted-β-amino-α-oxopropionic acid moiety of poststatin analogues for endopeptidase inhibitory activity. The analogue in which the D-leucine residue of poststatin was replaced by L-leucine showed strong inhibitory activity to cathepsin B. Introduction of an aromatic group into the P₄ position and proline into the P₂ position increased inhibitory activity to elastase. Benzyloxycarbonyl-L-homophenylalanyl-(RS)-3-amino-2-oxovaleryl-D-leucyl-L-valine was about 6 times more active to prolyl endopeptidase than natural poststatin.