Synthesis of some pseudo-peptide analogs of thiol proteinase inhibitors

Some pseudo-peptide analogs of thiol proteinase inhibitors were synthesized by a conventional solution method. Among them, Suc-Ala-Val-Val-Ala-psi-(CH 2-NH)-Ala-pNA (peptide 1) and Suc-Ala-Val-Val-psi-(CH2NH)-Ala-Ala-pNA (pept ide 2) showed a stronger inhibitory activity compared with parent peptide s uch as Suc-Ala-Val-Val-Ala-Ala-pNA. In particular, peptide 2 was about 10-f old as active as the parent peptide (IC50=8 mu M). Inserting psi-(CH2-NH) p ossibly makes the inhibitor less susceptible to papain and, as a result, pr oduces more potent inhibition.