Stereoselectivity and affinity in molecular pharmacology. IV. A search for eudismic-affinity correlations among angiotension II analogues.
In order to establish the applicability of eudismic analysis (correlation between potency and the ratio of isomer potencies), the extensive data reported on the biological activities of angiotensin II analogues were examined. For a series of 13 heptapeptides epimeric at the N-terminal residue, apparent correlations were found for pressor activity in vivo, but not for 10 of them on the basis of their myotropic activity under in vitro conditions. The analogues belongning to sub-groups displaying correlations have side chains of sufficiently different nature so that their grouping is questionable. 3 octapeptides epimeric at the second residue displayed an excellent correlation for their pressor activity. The demonstrated differential metabolic susceptibility of these epimers, however, casts further doubt on the usefulness of the data as a measure of their potency. The lack of a correlation under in vitro conditions would indicate that eudismic-affinity correlations (EAC) may be limited to epimers which differ less in their properties than these angiotensin analogues. Nevertheless, until better receptor affinity estimates become available, the observed correlations may be useful in advancing our knowledge of the angiotensin II receptor in particular, and of stereoselective molecular recognition in general.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008968:Molecular Conformation; D009132:Muscles / Q000187:drug effects; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000804:Angiotensin II