Poststatin, a new inhibitor of prolyl endopeptidase .6. Endopeptidase inhibitory activity of poststatin analogues containing pyrrolidine ring

Several pyrrolidine-containing analogues of poststatin were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Replacement of the postine residue with 2-oxo-2-(2-pyrrolidinyl)acetic acid increased the selectivity and inhibitory activity against prolyl endopeptidase. Benzyloxycarbonyl-L-phenylalanyl-(S)-2-oxo-2-(2-pyrrolidinyl)acetyl-D-phenyl-alanine alanine was about 46 times as active to prolyl endopeptidase as natural poststatin.