Novel peptides with orally active and long-lasting antihypertensive activity.

A series of N-(P-substituted phosphinoyl)peptides were synthesized and their antihypertensive activities were tested in spontaneously hypertensive rats (SHR). Among them, N-(dibenzyloxyphosphinoyl)-L-Ala-L-Pro-L-Pro-OH showed the most potent and long-lasting antihypertensive activity in SHR when administered orally. Although the inhibitory activity of this peptide against the angiotensin-converting enzyme was about one-hundredth of that of Captopril, the antihypertensive activity in SHR was significantly higher and longer-lasting than that of Enalapril which has been reported to be the most potent agent among similar converting enzyme inhibitors.