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 |
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Authors: | Prabhu Arati Malde Alpeshkumar Coutinho Evans Srivastava Sudha |
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Institution: | Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, India. |
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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. |
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