Structure–Activity Relationships of a Series of Analogues of the RFamide-Related Peptide 26RFa - Normandie Université Access content directly
Journal Articles Journal of Medicinal Chemistry Year : 2011

Structure–Activity Relationships of a Series of Analogues of the RFamide-Related Peptide 26RFa

Abstract

26RFa is a new member of the RFamide peptide family that has been identified as the endogenous ligand of the orphan GPCR GPR103. As the C-terminal heptapeptide (26RFa((20-26))) mimics the action of the native peptide on food intake and gonadotropin secretion in rodents, we have synthesized a series of analogues of 26RFa((20-26)) and measured their potency to induce [Ca(2+)](i) mobilization in Gα(16)-hGPR103-transfected CHO cells. Systematic replacement of each residue by an alanine (Ala scan) and its D-enantiomer (D scan) showed that the last three C-terminal residues were very sensitive to the substitutions while position 23 tolerated rather well both modifications. Most importantly, replacement of Ser(23) by a norvaline led to an analogue, [Nva(23)]26RFa((20-26)), that was 3-fold more potent than the native heptapeptide. These new pharmacological data, by providing the first information regarding the structure-activity relationships of 26RFa analogues, should prove useful for the rational design of potent GPR103 receptor ligands with potential therapeutic application.
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Dates and versions

hal-01962818 , version 1 (20-12-2018)

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Olivier Le Marec, Cindy Neveu, Benjamin Lefranc, Christophe Dubessy, Jean A. Boutin, et al.. Structure–Activity Relationships of a Series of Analogues of the RFamide-Related Peptide 26RFa. Journal of Medicinal Chemistry, 2011, 54 (13), pp.4806-4814. ⟨10.1021/jm200418c⟩. ⟨hal-01962818⟩
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