Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose

T. Tsuzuki, S. Takano, N. Sakaguchi, T Kudoh, Takashi Murayama, Takashi Sakurai, Haruhiro Higashida, K Weber, A H Guse, T. Kameda, T. Hirokawa, Y. Kumaki, M Arisawa, Barry Potter, Satoshi Shuto

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Abstract

Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, 3), designed as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative 8 and the 4-thioribosylamine 7 via equilibrium in 7 between the α-anomer (7α) and the β-anomer (7β) during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca2+ like cADPR in various biological systems, such as sea urchin homogenate, NG108-15 neuronal cells, and Jurkat T-lymphocytes. Thus, cADPtR is a stable equivalent of cADPR, which can be useful as a biological tool for investigating cADPR-mediated Ca2+-mobilizing pathways.
Original languageEnglish
Pages (from-to)35-51
Number of pages17
JournalMessenger
Volume3
Issue number1-2
DOIs
Publication statusPublished - Jun 2015

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    Tsuzuki, T., Takano, S., Sakaguchi, N., Kudoh, T., Murayama, T., Sakurai, T., Higashida, H., Weber, K., Guse, A. H., Kameda, T., Hirokawa, T., Kumaki, Y., Arisawa, M., Potter, B., & Shuto, S. (2015). Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose. Messenger, 3(1-2), 35-51. https://doi.org/10.1166/msr.2014.1035