NMR AND MOLECULAR MODELING INVESTIGATIONS OF THE NEUROPEPTIDE BRADYKININ IN 3 DIFFERENT SOLVENT SYSTEMS - DMSO, 9 1 DIOXANE/WATER, AND IN THE PRESENCE OF 7.4 MM LYSO PHOSPHATIDYLCHOLINE MICELLES/

The linear nonapeptide hormone bradykinin )-Pro(2)-pro(3)-Gly(4)-Phe(5 )-Ser(6)-pro(7)-Phe(8) Arg(9)) is involved, either directly or indirec tly, in a wide variety of physiological processes, particularly pain a nd hyperanalgesia. Additional evidence suggests that bradykinin also p lays a major role in inflammatory response, asthma, sepsis, and sympto ms associated with the rhinoviral infection. It has long been speculat ed that a beta-turn the C-terminus of bradykinin plays a major role in the biological activity of the neuropeptide. The beta-turn forming po tential of bradykinin in three vastly different local chemical environ ments, DMSO, 9 : 1 dioxane/water, and in the presence of 7.4 mM lyse p hosphatidylcholine micelles, was investigated using two-dimensional ho monuclear nmr experiments coupled with simulated annealing calculation s. The results of these investigations show that in all three systems residues 6-9 of the C-terminus adopt very similar beta-turn like struc tures. These results suggest that the beta-turn at the C-terminus of b radykinin is an important secondary structural feature for receptor re cognition and binding. (C) 1994 John Wiley and Sons, Inc.