A ring-reversed analog of atrial natriuretic peptide retains receptor binding, guanylate cyclase stimulation.
We have prepared an atrial natriuretic peptide analog, ANP[13-27][1-12], in which the connectivity of the disulfide-linked ring has been reversed by formally cleaving the ring and cyclizing the N- and C-terminal tails. This analog, which retains many of the spatial relationships of the native molecule, binds to both ANP-A and ANP-C receptor subtypes, and triggers the production of cyclic-GMP by ANP-A. ANP-C binding of ANP[13-27][1- 12] is roughly equipotent to that of ANP itself, although the ring cleavage falls within the putative ANP-C binding domain. ANP[13-27][1-8], a truncated analog in which much of this binding domain has been removed, surprisingly maintains a high affinity for ANP-C; however, this peptide has lost the ability to activate the ANP-A-linked guanylate cyclase.
von Geldern
T W
TW
Cardiovascular Research Division, Abbott Laboratories, IL 60064.
Budzik
G P
GP
Dillon
T P
TP
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000737:chemistry* / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D015195:Drug Design; D004730:Endothelium, Vascular / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship
D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP