Probing the role of proline in peptide hormones. NMR studies of bradykinin and related peptides.

Abstract

The use of NMR methods to study conformational and dynamic aspects of the proline residues in the nonapeptide bradykinin is reviewed. NMR analyses involve considerations of bistable equilibria which include the cis/trans conformational heterogeneity of the imide bond, the cis'/trans' regions of conformational stability which characterize rotation about the C alpha-CO bond (dihedral angle psi), and the interconversion of the pyrrolidine ring of proline between puckered C gamma-endo and C gamma-exo conformations. These conformational features are all characterized by different kinetic behavior, are interdependent with peptide bond conformation, and exhibit sensitivity to amino acid substitutions. Thus, the substitution of Gly6 for Ser6 increases the fractional cis probability of the sixth peptide bond from 0.1 to 0.35. Substitutions of alpha-aminoisobutyric acid (AIB) residues for proline introduce conformational constraints analogous to those in cis' proline. Correlations of pyrrolidine ring conformation and dynamics with the cis/trans ratio of the imide bond have also been observed in model systems. Conformational and activity analyses of [AIB7]-bradykinin provided a stimulus for the development of the first bradykinin antagonist by Stewart and Vavrek (Vavrek RJ and Stewart JM, Competitive antagonists of bradykinin. Peptides 6: 161-164, 1985).

Cite this paper

@article{London1990ProbingTR, title={Probing the role of proline in peptide hormones. NMR studies of bradykinin and related peptides.}, author={Robert E. London and John M Stewart and John Cann}, journal={Biochemical pharmacology}, year={1990}, volume={40 1}, pages={41-8} }