Investigation of the spatial structure of a cyclic analog of bradykinin in solution by two-dimensional NMR spectroscopy

Assignment of the 1H NMR signals of [cyclo(9 → 1/sup epsilon/), Lys1, Gly6]bradykinin (CBK) in (CD3)2SO and H2O has been made by the combined analysis of two-dimensional COSY and NOESY spectra. It has been shown that in (CD3)2SO solution there are two slowly interchanging conformers of CBK; the amount of the minor conformer does not exceed 15%. In aqueous solution the minor conformer is absent, and the chemical shifts of the NH and CsupαH protons of CBK and of the natural peptide differ insignificantly. Models are proposed of the spatial structure of the backbone of fragments 6-9 of CBK, which contain two intramolecular hydrogen bonds with the participation of the NH group of the Arg9 residue, the N/sup zeta/H group of the Lys1 residue, and the carbonyl groups of the Phe5 and Gly6 residues