Further Studies at Neuropeptide S Position 5: Discovery of Novel Neuropeptide S Receptor Antagonists

摘要

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 [Ca2+](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 ['Bu-D-Gly(5)]NPS.