Role of the C-terminal carboxylate in angiotensin II activity: alcohol, ketone, and ester analogs of angiotensin II

Publisher Website
Google Scholar
Abstract
[Ac-Asn1,Val5]angiotensin II analogues containing a C-terminal alcohol (Phe-ol), methyl ketone (Pmk), methyl ester (Phe-OMe) or .alpha.-methyl methyl ester (Phe(.alpha.Me)-OMe) were prepared in order to examine the relative importance of COOH-mediated ionic vs.hydrogen bonding interactions in angiotensin activities. Based on the observation that only [Ac-Asn1,Phe-OM8]AII (AII, angiotensin II) had significant activities (20% oxytocic and 13% pressor) in the rat, with all other analogues having negligible agonistic and antagonistic effects, it is concluded that ionic interaction of the C-terminal carboxylate with the receptor is necessary for angiotensin binding and that hydrogen bonding has little effect. Thus, the different potencies observed for the AII methyl ester and for various C-terminal analogues previously reported may simply reflect their relative abilities to generate the active carboxylate species in situ.