Peptide analogues of angiotensinogen. Effect of peptide chain length on renin inhibition.

Renin inhibition was evaluated for a series of peptide analogues of angiotensinogen with different chain lengths. Systematic deletion of amino acid residues from the hexapeptide BocPheHisLeuR-ValIleHisOCH3 showed that the presence of residues at the N-terminal Phe and His positions was essential for efficient enzyme-inhibitor binding whereas the C-terminal Ile and His residues were much less important. Synthesis of a tetrapeptide analogue shortened at the C-terminus and containing modified side chains produced a potent inhibitor of renin which demonstrated hypotensive activity in a salt depleted monkey.