Amino acids and peptides. LIII. Synthesis and biological activities of some pseudo-peptide analogs of PKSI-527, a plasma kallikrein selective inhibitor: The importance of the peptide backbone

Pseudo-peptide analogs of trans-4-aminomethylcyclohexanecarbonyl-L-phenylal anyl-4-aminophenyl acetic acid (PKSI-527, plasma kallikrein selective inhib itor), in which an amide bond (peptide bond) has been replaced by a CH2-NH bond, ie, trans-4-aminomethylcyclohexanecarbonyl-L-phenylalanyl-psi(CH2-NH) -4-aminophenyl acetic acid (I), trans-4-aminomethylcyclohexanecarbonyl-psi( CH2-NH)-L-phenylalanyl-4-aminophenyl acetic acid (II) and trans-4-aminometh ylcyclohexanecarbonyl-D-phenylalanyl-psi(CH2-NH)-4-aminophenyl acetic acid (III) were synthesized, These pseudo-peptide analogs did not exhibit any de tectable inhibitory activity against plasma kallikrein (PK), plasmin (PL), urokinase (UK), thrombine (TH) or trypsin (TRY), These results indicate tha t both carbonyl groups in the PKSI-527 are important for the manifestation of potent inhibitory activity against plasma kallikrein.