NMR AND MOLECULAR MODELING INVESTIGATIONS OF THE NEUROPEPTIDE SUBSTANCE-P IN THE PRESENCE OF 15-MM SODIUM DODECYL-SULFATE MICELLES

To better understand the structural basis of the biological activity o f the neuropeptide substance P SP; (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gl y-Leu-Met-NH2), two-dimensional nmr spectroscopy experiments and simul ated annealing calculations were used to investigate the conformation adopted in the presence of the membrane model system sodium dodecyl su lfate. It was determined that SP in the presence of SDS micelles under goes a conformational equilibrium between an alpha- and a 3(10)-helix involving the midregion (Pro(4)-Gln(5)- Gln(6)-Phe(7)-Phe(8)) of the p eptide. The C-terminus adopts an extended conformation while the N-ter minus remains quite flexible. The conformation adopted by SP in the pr esence of SDS micelles yields a structure that is consistent with the model of a neurokinin-1 selective ligand proposed by Convert. (C) 1994 John Wiley and Sons, Inc.