Pharmacological profile of 8-amino octanoic acid substituted atrial natriuretic factor analogs.
A series of six analogs of rat atrial natriuretic factor have been prepared by the solid-phase method. The modified analogs contain 8-amino octanoic acid (a simple alkyl spacer) in place of selected tripeptides. Binding affinity to cultured aortic smooth muscle cell membranes suggests that the sequence Arg11-Gly16 is important for binding. Vasorelaxant activity on serotonin contracted rabbit aortic rings indicates that the Phe8-Gly16 sequence must be present for vasorelaxation. In anesthetized rats, the natriuretic and diuretic effects of an IV bolus dose correlate with in vitro vasodilatory activity. The alkyl spacer approach provides a facile method to quickly determine key regions of a large peptide involved in molecular recognition.
Hassman
C F
CF
Merrell Dow Research Institute, Cincinnati, OH 45215.
Pelton
J T
JT
Buck
S H
SH
Shea
P
P
Heminger
E F
EF
Broersma
R J
RJ
Berman
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001667:Binding, Competitive; D004231:Diuresis / Q000187:drug effects; D008969:Molecular Sequence Data; D009318:Natriuresis / Q000187:drug effects; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
D009320:Atrial Natriuretic Factor