Development of a selective peptide antagonist for the human natriuretic peptide receptor-B.

Julie Deschênes (1) , Cécile Duperé (1) , Normand Mcnicoll (1) , Nicholas L'Heureux (2) , François Auger (2) , Alain Fournier (3) , André de Léan (1)

1 Department of pharmacology, Faculty of Medicine
2 Laboratory of Experimental Organogenesis, Hopital St-Sacrement
3 INRS-IAF - Institut Armand Frappier

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.

Domaines: Toxicologie

Julie Deschênes, Cécile Duperé, Normand Mcnicoll, Nicholas L'Heureux, François Auger, et al.. Development of a selective peptide antagonist for the human natriuretic peptide receptor-B.. Peptides, 2005, 26 (3), pp.517-24. ⟨10.1016/j.peptides.2004.10.017⟩. ⟨pasteur-00820035⟩