title: 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.
abstract: 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 beta-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.
authors.affiliation: Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, India.
authors.forename: Arati
authors.initials: A
authors.lastname: Prabhu
authors.forename: Alpeshkumar
authors.initials: A
authors.lastname: Malde
authors.forename: Evans
authors.initials: E
authors.lastname: Coutinho
authors.forename: Sudha
authors.initials: S
authors.lastname: Srivastava
mesh_terms: D002942:Circular Dichroism; D003198:Computer Simulation; D004151:Dipeptides / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry* / Q000494:pharmacology; D012996:Solutions; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004151:Dipeptides; D007211:Indoles; D011994:Recombinant Proteins; D012996:Solutions; C078949:FK 888; D013373:Substance P; C032132:substance P, prolyl(2)-tryptophan(7,9)-; C050702:substance P, Arg(1)-Pro(2)-Trp(7,9)-Leu(11)-; C042867:spantide