NMR-STUDY OF 5 N-TERMINAL PEPTIDE-FRAGMENTS OF THE VASOACTIVE-INTESTINAL-PEPTIDE - CRUCIAL ROLE OF AROMATIC RESIDUES

Five peptides related to the N-terminal sequence of the vasoactive int estinal peptide (VIP) have been synthesized. Two-dimensional nuclear m agnetic resonance (2D-NMR) experiments (i.e., correlated spectroscopy [COSY]) and low-temperature coefficient measurements for particular NH chemical shifts suggest the presence of hydrogen bondings in both VIP (1-7) and VIP(1-11) fragments. Nuclear overhauser enhancement spectro scopy (NOESY) show that aromatic interactions stabilize a preferred co nformation. The crucial role of the first histidine residue, which is a determinant for the biological activity, is explained by specific in teractions with the aromatic protons of Phe(6) and Tyr(10).