CONFORMATION AND SELF-ASSOCIATION OF THE PEPTIDE-HORMONE SUBSTANCE-P - FOURIER-TRANSFORM INFRARED SPECTROSCOPIC STUDY

Fourier-transform i.r. (f.t.i.r.) spectroscopy has been applied to the study of the conformational properties of substance P in aqueous solution. Spectra were obtained in the presence of lipid membranes and Ca2+ to assess the role of these factors in induction of the active conformation of the peptide. In aqueous solution substance P was found to be predominantly unstructured at physiological p(2)H. where the lack of long-range order is probably related to charge repulsion along the peptide chain. However, substance P aggregated in aqueous solution at p(2)H > 10.0. Little or no induction of secondary structure was seen on addition of the peptide to negatively charged bilayers, suggesting that interaction with a membrane surface does not play an important role in the stabilization of the active conformation of the peptide. In fact, substance P was found to aggregate in the presence of charged lipids, which would tend to hinder rather than enhance interaction with the receptor. We propose a model for the aggregation of substance P at the bilayer surface, based on our studies of the effect of p(2)H and lipid/peptide ratio on spectra. Addition of Ca2+ had no effect upon the secondary structure of the peptide or on its interactions with membranes.