Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists

J Med Chem. 2009 Jul 9;52(13):4068-71. doi: 10.1021/jm900604g.

Abstract

Neuropeptide S (NPS) regulates various biological functions by activating the NPS receptor (NPSR). Previous studies demonstrated that the substitution of Gly(5) with d-amino acids generates NPSR antagonists. Eleven [d-Xaa(5)]NPS derivatives were synthesized and pharmacologically tested measuring [Ca(2+)](i) in HEK293(mNPSR) cells. The results confirmed that the [d-Xaa(5)] substitution promotes antagonist activity with potency inversely related to the side chain size and allowed identification of the novel potent NPSR peptide antagonist [(t)Bu-d-Gly(5)]NPS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / analysis
  • Cell Line
  • Drug Discovery
  • Humans
  • Neuropeptides / chemistry*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • NPSR1 protein, human
  • Neuropeptides
  • Receptors, G-Protein-Coupled
  • neuropeptide S, human
  • Calcium