Solution conformation of Substance P antagonists-[d-Arg1, d-Trp7,9, Leu11]-SP, [d-Arg1, d-Pro2, d-Trp7,9, Leu11]-SP and [d-Pro2, d-Trp7,9]-SP by CD, NMR and MD simulations

Substance P (SP) is an important neuropeptide involved in pain transmission and induction of inflammation. Its antagonists are being extensively investigated for their non-narcotic analgesic and anti-inflammatory activity. With a view towards better understanding the structural requirements of these analogs for efficient interaction with the SP receptor, the conformation of three SP antagonists [d-Arg1, d-Trp7,9, Leu11]-SP, [d-Arg1, d-Pro2, d-Trp7,9, Leu11]-SP and [d-Pro2, d-Trp7,9]-SP has been studied by CD, NMR and molecular dynamics (MD) simulations. All three peptides exhibit a high dependence of structure on the solvent. The molecules tend to adopt β-turns in solvents like DMSO and H2O and form helices in a hydrophobic environment. A direct relation between the helix forming potential of these antagonists with their receptor binding potency has been observed.