Mutations in B-type natriuretic peptide mediating receptor-A selectivity

Libraries of monovalent display-phage expressing mutant human B-type natriuretic peptide (hBNP) mere used to identify variants that preferentially bind natriuretic peptide receptor-A (NPR-A) compared to receptor-C (NPR-C), Position 19 was a significant determinant of receptor specificity for hBNP display phage. The synthetic hBNP variant S19R had a 265-fold improved NPR-A binding over NPR-C, analogous to the atrial natriuretic peptide (ANP) specificity mutation G16R, Mutation of the last three residues of the hBNP disulfide ring, G23F/ L24W/G25R, resulted in about 9-fold improved selectivity, The analogous mutations in ANP decreased NPR-A binding, suggesting divergence in the mechanism of NPR-A recognition. (C) 1997 Federation of European Biochemical Societies.