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 solu tion. Spectra were obtained in the presence of lipid membranes and Ca2 + to assess the role of these factors in induction of the active confo rmation of the peptide. In aqueous solution substance P was found to b e predominantly unstructured at physiological p(2)H. where the lack of long-range order is probably related to charge repulsion along the pe ptide 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 tha t interaction with a membrane surface does not play an important role in the stabilization of the active conformation of the peptide. In fac t, substance P was found to aggregate in the presence of charged lipid s, which would tend to hinder rather than enhance interaction with the receptor. We propose a model for the aggregation of substance P at th e bilayer surface, based on our studies of the effect of p(2)H and lip id/peptide ratio on spectra. Addition of Ca2+ had no effect upon the s econdary structure of the peptide or on its interactions with membrane s.