ANGIOTENSIN-2 ANALOGS .I. SYNTHESIS AND BIOLOGICAL EVALUATION OF [GLY1,GLY2,ILE5]-ANGIOTENSIN-2, [AC-GLY1,GLY2,ILE5]-ANGIOTENSIN-2, AND [GLY1,GLY2,ILE5,HIS(BZL)6]-ANGIOTENSIN-2

[Gly1,Gly2,Ile5]-angiotensin II has been synthesized by fragment condensation and also in better yield and purity by solid-phase synthesis. This peptide showed 16-20% of the pressor activity of [Asn1,Val5]-angiotensin II in the rat and the dog, while its N-acetyl derivative showed an activity of 0.4%. These results show that only a single basic group is necessary in the N-terminal dipeptide for good pressor potency. This essential basic group may be correlated with either the terminal amino group or the guanido group of arginine in angiotensin II. The low activity of the acetylated peptide shows that extension of the peptide backbone from six to eight amino acids does not alone contribute measurably to the potency of natural angiotensin II. The synthetic intermediate [Gly1,Gly2,Ile5,His(Bzl)6]-angiotensin II showed a pressor activity of 0.3% indicating the importance of the free imidazole ling. © 1969, American Chemical Society. All rights reserved.