Conformation of cyclobradykinin by nmr and distance geometry calculations

The conformation of the head-to-tail cyclic analogue of bradykinin in DMSO was investigated by nmr. Three sets of resonances were detected and fully assigned. These were attributed to the presence of three stable conformers, two of which were exchanging on the nmr time scale. A fourth, incomplete set of resonances was detected but not assigned. The three major conformers differ in the conformation at the three X-Pro bonds present. From nuclear Overhauser effect spectroscopy (NOESY) spectra, three sets of interproton distances were derived and used in NOE-restrained distance geometry calculations. The resulting structures were refined by energy minimization to yield families of structures. Conformer I is characterized by the presence of two type VIb beta-turns between Arg1 and Gly4 and between Phe5 and Phe8. The first beta-turn is present also in conformer II, while an inverse gamma-turn bridging Pro3 is the most pronounced structural feature of conformer III.