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

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.

SUBMITTER: Guerrini R

PROVIDER: S-EPMC2732566 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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

Guerrini Remo R Camarda Valeria V Trapella Claudio C Caló Girolamo G Rizzi Anna A Ruzza Chiara C Fiorini Stella S Marzola Erika E Reinscheid Rainer K RK Regoli Domenico D Salvadori Severo S

Journal of medicinal chemistry 20090701 13

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 ...[more]

PMID: 19473027

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