title: Development of a selective peptide antagonist for the human natriuretic peptide receptor-B.
abstract: Activation by C-type natriuretic peptide (CNP) of its receptor NPRB results in venodilation and inhibition of cellular proliferation. NPRB-selective antagonists should be useful to understand their physiological implications. We previously observed that [Thr9,Ser11,Arg16](N,C-ANP)pBNP (P12) is an antagonist for bNPRB and a potent agonist for bNPRA. The antagonist [Ser11](N-CNP,C-ANP)pBNP(2-26) (P18) displays six-fold selectivity towards hNPRB versus hNPRA. Deletion of the C-terminus in [Ser11](N-CNP,C-ANP)pBNP(2-25) (P19) decreases its affinity for hNPRA but improves its selectivity 35-fold. Peptide libraries based on P19 using phage display methodology yielded two positive clones P20 and P21. P19 behaves as the most potent antagonist, but P20 is the most selective.
authors.affiliation: Department of pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Qc, Canada, H3T 1J4.
authors.forename: Julie
authors.initials: J
authors.lastname: Deschênes
authors.forename: Cécile
authors.initials: C
authors.lastname: Duperé
authors.forename: Normand
authors.initials: N
authors.lastname: McNicoll
authors.forename: Nicholas
authors.initials: N
authors.lastname: L'Heureux
authors.forename: François
authors.initials: F
authors.lastname: Auger
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: André
authors.initials: A
authors.lastname: De Léan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D019556:COS Cells; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000473:pathology; D006162:Guanylate Cyclase / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D045283:Natriuretic Agents / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000737:chemistry; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D018000:Receptors, Peptide / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D006152:Cyclic GMP; D006162:Guanylate Cyclase; D045283:Natriuretic Agents; D009419:Nerve Tissue Proteins; D019151:Peptide Library; D010455:Peptides; D017461:Receptors, Atrial Natriuretic Factor; D018000:Receptors, Peptide; D000099242:Atrial Natriuretic Factor Receptor B; C073616:atrial natriuretic factor receptor C