Rouméas Laurent, Humbert Jean-Paul, Schneider Séverine, Doebelin Christelle, Bertin Isabelle, Schmitt Martine, Bourguignon Jean-Jacques, Simonin Frédéric, Bihel Frédéric
University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch Graffenstaden, France.
University of Strasbourg, CNRS, UMR7242, ESBS, 67412 Illkirch Graffenstaden, France.
Peptides. 2015 Sep;71:156-61. doi: 10.1016/j.peptides.2015.07.016. Epub 2015 Jul 23.
Mammalian RF-amide peptides including RF-amide-related peptides-1 and -3, neuropeptides AF and FF, Prolactin releasing peptides, Kisspeptins and RFa peptides are currently considered endogenous peptides for the GPCRs NPFF1R, NPFF2R, GPR10, GPR54 and GPR103, respectively. While NPFF1R and NPFF2R displayed high affinity for all the RF-amide peptides, GPR10, GPR54 and GPR103 only bind their cognate ligands. Through a systematic and sequential N-terminus deletion and benzoylation of either RF-amide neuropeptide (RFRP-3, NPFF, Kp-10, PrRP20, and 26RFa), we report the corresponding impact on affinity and activity towards all the RF-amide receptors (NPFF1R, NPFF2R, GPR10, GPR54 and GPR103). Our results highlight the difficulty to develop selective peptide ligands for GPR10, GPR54 or GPR103 without a modification of the C-terminus RF-amide signature, but open the door to the design of new RF-amide peptides acting as agonist for one receptor and antagonist for another one.
包括相关RF-酰胺肽-1和-3、神经肽AF和FF、催乳素释放肽、亲吻素和RFa肽在内的哺乳动物RF-酰胺肽，目前分别被认为是GPCRs NPFF1R、NPFF2R、GPR10、GPR54和GPR103的内源性肽。虽然NPFF1R和NPFF2R对所有RF-酰胺肽都表现出高亲和力，但GPR10、GPR54和GPR103仅结合其同源配体。通过对RF-酰胺神经肽（RFRP-3、NPFF、Kp-10、PrRP20和26RFa）进行系统的、连续的N端缺失和苯甲酰化，我们报告了其对所有RF-酰胺受体（NPFF1R、NPFF2R、GPR10、GPR54和GPR103）亲和力和活性的相应影响。我们的结果突出了在不修饰C端RF-酰胺特征的情况下，开发针对GPR10、GPR54或GPR103的选择性肽配体的困难，但为设计新型RF-酰胺肽打开了大门，这些肽可作为一种受体的激动剂和另一种受体的拮抗剂。
