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Published: 2017-02-22

Synthesis and Ability of New Ligands for G Protein-Coupled Receptors 17 (GPR17)

Tongyou Zhuo, Shengxue Zhou, Wei Zhang, Catia Lambertucci, Rosaria Volpini

(School of Food Technology, Jilin Agricultural Science and Technology College, Jilin City, Jilin, China (mainland))

Med Sci Monit 2017; 23:953-959

DOI: 10.12659/MSM.902048


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.

Keywords: Affinity Labels, Chromatography, Affinity, Gas Chromatography-Mass Spectrometry



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