Synthesis and biological activity of human neuropeptide S analogues modified in position 2

Journal of Medicinal Chemistry
Valeria CamardaS Salvadori

Abstract

Neuropeptide S (NPS) has been identified as the endogenous ligand of a previously orphan receptor now named NPSR. Previous studies demonstrated that the N-terminal sequence Phe (2)-Arg(3)-Asn(4) of the peptide is crucial for biological activity. Here we report on a focused structure-activity study of Phe(2) which has been replaced with a series of coded and noncoded amino acids. Thirty-one human NPS analogues were synthesized and pharmacologically tested for intracellular calcium mobilization by using HEK293 cells stably expressing the mouse NPSR. The results of this study demonstrated the following NPS position 2 structure-activity features: (i) lipophilicity but not aromaticity is crucial, (ii) both the size of the chemical moiety and its distance from the peptide backbone are important for biological activity, and (iii) this position plays a role in both receptor binding and activation, since [4,4'-biphenyl-Ala(2)]hNPS behaved as a partial agonist.

References

Aug 18, 2004·Neuron·George F Koob, Thomas N Greenwell
Jan 5, 2005·Trends in Pharmacological Sciences·Olivier Civelli
Sep 8, 2005·The Journal of Pharmacology and Experimental Therapeutics·Rainer K ReinscheidOlivier Civelli

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Citations

Nov 1, 2013·Journal of Medicinal Chemistry·Samarjit PatnaikChristopher P Austin
May 29, 2009·Journal of Medicinal Chemistry·Remo GuerriniSevero Salvadori
Oct 31, 2008·The Journal of Pharmacology and Experimental Therapeutics·Valeria CamardaGirolamo Calò
May 27, 2014·General and Comparative Endocrinology·Ravisankar Valsalan, Narayanan Manoj
Aug 19, 2015·Clinical and Experimental Pharmacology & Physiology·Jamylle Nunes de Souza FerroEmiliano Barreto
Jul 7, 2010·Peptides·Ya-Li PengRui Wang
Oct 14, 2009·Medicinal Research Reviews·Remo GuerriniGirolamo Calo'
Sep 17, 2008·Bioorganic & Medicinal Chemistry·Valeria CamardaSevero Salvadori
Apr 1, 2011·ChemMedChem·Diego Dal BenGloria Cristalli
Jan 21, 2010·ChemMedChem·Diego Dal BenGloria Cristalli
Feb 19, 2015·Pharmacology Research & Perspectives·Chiara RuzzaRemo Guerrini
Dec 12, 2018·Pharmacology Research & Perspectives·Chiara RuzzaGirolamo Calo
May 1, 2021·Pharmaceuticals·Rainer K Reinscheid, Chiara Ruzza

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