Superactive analogs of the atrial natriuretic peptide (ANP).
Three analogs of the atrial natriuretic peptide ANP(105-126), lacking the N-terminal exocyclic peptide segment and containing 2-mercaptoacetic acid, 3-mercaptopropionic acid or 4-mercaptobutyric acid in place of the cysteine residue in position 105 of the peptide sequence, were synthesized by the solid-phase method. The resulting des-amino analogs showed 2 to 4 times higher diuretic/natriuretic activity than the most active natural ANP and displayed a potent hypotensive effect as well. All three analogs were relatively less potent in various in vitro bioassays and in a binding assay, indicating that their high activities in vivo may be due to resistance to enzymatic degradation and to reduced non-specific tissue adsorption. These compounds not only will serve as useful pharmacologic tools but also represent prototypes for the development of further reduced-size ANP analogs.
D000302:Adrenal Cortex / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D004231:Diuresis / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D009318:Natriuresis / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents
D014665:Vasodilator Agents; D000450:Aldosterone; D009320:Atrial Natriuretic Factor