title: Synthesis and Ability of New Ligands for G Protein-Coupled Receptors 17 (GPR17).
abstract: GPR17 is believed to be a novel target for the development of new therapeutic approaches to human stroke and multiple sclerosis. Hence, the selection of GPR17 ligands may be a potent way to reduce the progression of ischemic damage. New potential ligands for GPR17, mono-, di-, and triphosphate adenosine nucleotides substituted at N6-position with a methyl and a cyclopentyl group were synthesized. The ability of new ligands to bind GPR17 was evaluated using frontal affinity chromatography-mass spectrometry (FAC-MS) method. Cangrelor, MRS2179, and uridine diphosphate were selected as the reference compounds. The new triphosphate derivatives 9 and 10 were considered as the new GPR17 ligands. The compound 10 was eluted with breakthrough time (bt) between cangrelor and MRS 2179 (compound 10, bt=12.25; cangrelor, bt=24.55, and MRS 2179, bt=7.10), while the breakthrough volume of compound 9 was similar to that of MRS 2179 (compound 9, bt=7.53 and MRS 2179, bt=7.10). N6-cyclopentyATP 10 is medium-high affinity ligand of GPR17, while the corresponding N6-methyl derivative 9 is a medium affinity ligand similar to MRS 2179. Hence, the new N6-cyclopentylATP 10 might be a good candidate for the pharmacological characterization of GPR17.
authors.affiliation: School of Food Technology, Jilin Agricultural Science and Technology College, Jilin City, Jilin, China (mainland).
authors.forename: Tongyou
authors.initials: T
authors.lastname: Zhuo
authors.affiliation: College of Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin City, Jilin, China (mainland).
authors.forename: Shengxue
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Changchun Beihua Pharmaceutical Co., Jilin City, Jilin, China (mainland).
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: University of Camerino, Camerino, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Lambertucci
authors.affiliation: University of Camerino, Camerino, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002846:Chromatography, Affinity; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C121670:GPR17 protein, human; D055767:Immobilized Proteins; D008024:Ligands; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D043562:Receptors, G-Protein-Coupled; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor