Synthesis and activity of partial retro-inverso modified atrial natriuretic factor analogs.
The synthesis and pharmacological activity of partial retro-inverso modified rat atrial natriuretic factor (rANF) analogs is described. The route to these compounds utilized a combination of solution and solid-phase methods. The analogs prepared all contain a reversed amide bond (psi[NHCO]) at the Ser 25 to Phe26 linkage. This bond has been suggested to play a key role in the metabolic inactivation of ANF. The analogs are of comparable potency to the endogenous peptide rANF1-28 in binding to cultured rat vascular smooth muscle cells, in relaxing serotonin contracted rabbit aortic rings, and as natriuretic/diuretic agents in anesthetized rats. None of the peptides has an extended duration of action in vivo.
Berman
J M
JM
Merrell Dow Research Institute, Cincinnati, OH.
Pelton
J T
JT
Hassman
C F
CF
Buck
S H
SH
Shea
P J
PJ
Ertl
P
P
Heminger
E F
EF
Broersma
R J
RJ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000138:chemical synthesis* / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009318:Natriuresis / Q000187:drug effects; D009904:Optical Rotation; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
D007202:Indicators and Reagents; D009320:Atrial Natriuretic Factor