Role of the C-terminal carboxylate in angiotensin II activity: alcohol, ketone, and ester analogues of angiotensin II.
[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-OMe8]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.
D000438:Alcohols / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001665:Binding Sites; D004952:Esters / Q000494:pharmacology; D006860:Hydrogen Bonding; D007659:Ketones / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000187:drug effects; D013329:Structure-Activity Relationship
D000438:Alcohols; D004952:Esters; D007659:Ketones; D011945:Receptors, Angiotensin; D000804:Angiotensin II