10.1021/jm900604g.s001 Remo Guerrini Remo Guerrini Valeria Camarda Valeria Camarda Claudio Trapella Claudio Trapella Girolamo Caló Girolamo Caló Anna Rizzi Anna Rizzi Chiara Ruzza Chiara Ruzza Stella Fiorini Stella Fiorini Erika Marzola Erika Marzola Rainer K. Reinscheid Rainer K. Reinscheid Domenico Regoli Domenico Regoli Severo Salvadori Severo Salvadori Further Studies at Neuropeptide S Position 5: Discovery of Novel Neuropeptide S Receptor Antagonists American Chemical Society 2009 side chain size Novel Neuropeptide S Receptor AntagonistsNeuropeptide S NPSR peptide antagonist NPS receptor Previous studies Gly 5 HEK 293mNPSR cells substitution antagonist activity NPSR antagonists 2009-07-09 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Further_Studies_at_Neuropeptide_S_Position_5_Discovery_of_Novel_Neuropeptide_S_Receptor_Antagonists/2844406 Neuropeptide S (NPS) regulates various biological functions by activating the NPS receptor (NPSR). Previous studies demonstrated that the substitution of Gly<sup>5</sup> with d-amino acids generates NPSR antagonists. Eleven [d-Xaa<sup>5</sup>]NPS derivatives were synthesized and pharmacologically tested measuring [Ca<sup>2+</sup>]<sub>i</sub> in HEK293<sub>mNPSR</sub> cells. The results confirmed that the [d-Xaa<sup>5</sup>] substitution promotes antagonist activity with potency inversely related to the side chain size and allowed identification of the novel potent NPSR peptide antagonist [<sup><i>t</i></sup>Bu-d-Gly<sup>5</sup>]NPS.