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

Guerrini, Remo; Camarda, Valeria; Trapella, Claudio; Caló, Girolamo; Rizzi, Anna; Ruzza, Chiara; Fiorini, Stella; Marzola, Erika; Reinscheid, Rainer K.; Regoli, Domenico; Salvadori, Severo

doi:10.1021/jm900604g.s001

jm900604g_si_001.pdf (29.1 kB)

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

journal contribution

posted on 2009-07-09, 00:00 authored by Remo Guerrini, Valeria Camarda, Claudio Trapella, Girolamo Caló, Anna Rizzi, Chiara Ruzza, Stella Fiorini, Erika Marzola, Rainer K. Reinscheid, Domenico Regoli, Severo Salvadori

Neuropeptide S (NPS) regulates various biological functions by activating the NPS receptor (NPSR). Previous studies demonstrated that the substitution of Gly⁵ with d-amino acids generates NPSR antagonists. Eleven [d-Xaa⁵]NPS derivatives were synthesized and pharmacologically tested measuring [Ca²⁺]_i in HEK293_mNPSR cells. The results confirmed that the [d-Xaa⁵] substitution promotes antagonist activity with potency inversely related to the side chain size and allowed identification of the novel potent NPSR peptide antagonist [^tBu-d-Gly⁵]NPS.