Synthesis of analogues of pepstatin. Effect of structure in subsites P1', P2', and P2 on inhibition of porcine pepsin.

A series of pepstatin analogues having structural variations in the P2', P1', and P2 positions have been synthesized and tested for inhibition of porcine pepsin. The standard peptide for this study was Iva-Sta-Val-Ala-Iaa. Structural variations in the P2' and P1' positions have relatively little effect on Ki; however, small variations in the P2 position have a more dramatic effect on Ki and time-dependent inhibition. A series of pepstatin fragments were also synthesized and tested for inhibition of porcine pepsin.