Synthesis and pharmacological characterization of [125I]MRS1898, a high-affinity, selective radioligand for the rat A3 adenosine receptor |
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| Authors: | Zhan-Guo Gao Bao Teng Haitao Wu Bhalchandra V Joshi Gary L Griffiths Kenneth A Jacobson |
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| Institution: | (1) Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA;(2) Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, USA;(3) Present address: Nektar Therapeutics, Huntsville, AL 35801, USA |
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| Abstract: | A known selective agonist of the A3 adenosine receptors (AR), MRS1898 (1′R,2′R,3′S,4′R,5′S)-4-{2-chloro-6-(3-iodophenylmethyl)amino]purin-9-yl}-1-(methylaminocarbonyl)bicyclo3.1.0]hexane-2,3-diol], was synthesized in radioactive form and characterized pharmacologically. This agonist ligand series, based on nucleoside analogues containing a rigid, bicyclic ring system in place of the ribose moiety, was selected for radiolabeling due to its high A3AR affinity across species, with nanomolar binding at both rat and human A3ARs. The radioiodination of MRS1898 on its N6–3-iodobenzyl substituent was accomplished in 76% radiochemical yield by iododestannylation of a 3-(trimethylstannyl)benzyl precursor. 125I]MRS1898 bound to the rat A3AR with a Kd value of 0.17 | |
| Keywords: | Iodination G protein-coupled receptor Binding assay Purine Nucleoside Carbocyclic |
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