Novel Inhibitors of Human Renin. Cyclic Peptides Based on the Tetrapeptide Sequence Glu-D-Phe-Lys-D-Trp

Article abstract of DOI:10.1021/jm00171a033

Cyclic peptide inhibitors of human renin based on a linear peptide, Boc-D-Phe-Cys(Acm)-D-Trp-Leu-OMe (1), were prepared by solution-phase methods.Potent inhibitors were obtained in one series of compounds, (3), in which the D-phenylalanine residue was incorporated in a 15-membered ring structure.Any reductions or enlargements of the ring size led to inactive or less potent peptides.The most potent inhibitor of human renin, (31) (IC50 6.3 * 10^-8M), was obtained by changing N- and C-terminal parts of pentapeptide 3.It was about 650-fold more potent than linear tetrapeptide 1 and about 50-fold more potent than cyclic peptide 3.Compound 31 was also 112-fold more potent against human renin than against porcine renin.