Testing for cis' proline with alpha-aminoisobutyric acid substitution. N.m.r. studies of AIB substituted bradykinins.

Substitution of Pro residues with AIB (alpha-aminoisobutyric acid) residues in peptides provides a means of evaluating the presence of cis' proline conformations both in solution and, using bioassay data, in a receptor complex. 1H n.m.r. has been used to probe the DMSO solution conformation of all seven of the possible AIB/Pro isomers of bradykinin. AIB substitution for Pro2 and/or Pro3 appears to stabilize a type III beta-turn involving the N-terminal residues, but not an incipient 3(10) helix suggested by model peptides. These substitutions are correlated with low biological potencies, suggesting that such conformational features may be incompatible with receptor complexation. Alternatively, AIB7 -bradykinin analogs exhibit a variety of long range shift perturbations relative to bradykinin. The data suggests that bradykinin can adopt several folded conformations, including beta-turns involving both Ser6-Pro7-Phe8-Arg9 and Phe5-Ser6-Pro7-Phe8. The relatively high biological activities of the AIB7-BK suggest that the complexed form of the peptide is characterized by a cis' Pro7 conformation.