Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists.
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.
Guerrini
Remo
R
Department of Pharmaceutical Sciences and Biotechnology Center and Department of Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, National Institute of Neuroscience, Univ. of Ferrara, Ferrara, Italy. r.guerrini@unife.it
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
D002118:Calcium / Q000032:analysis; D002460:Cell Line; D055808:Drug Discovery; D006801:Humans; D009479:Neuropeptides / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C484532:NPSR1 protein, human; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled; C506531:neuropeptide S, human; D002118:Calcium