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

• Published in: Messenger (Los Angeles, Calif.) Vol. 3; no. 1-2; pp. 35 - 51
• Main Authors: Tsuzuki, Takayoshi, Takano, Satoshi, Sakaguchi, Natsumi, Kudoh, Takashi, Murayama, Takashi, Sakurai, Takashi, Hashii, Minako, Higashida, Haruhiro, Weber, Karin, Guse, Andreas H, Kameda, Tomoshi, Hirokawa, Takatsugu, Kumaki, Yasuhiro, Arisawa, Mitsuhiro, Potter, Barry V L, Shuto, Satoshi
• Format: Journal Article
• Language: English
• Published: United States 01.06.2014
• ISSN: 2167-955X; 2167-9568
• DOI: 10.1166/msr.2014.1035

Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, ), designed as a stable mimic of cyclic ADP-ribose (cADPR, ), a Ca -mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative and the 4-thioribosylamine via equilibrium in between the α-anomer ( ) and the β-anomer ( ) during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca 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 Ca -mobilizing pathways.