TY - JOUR
T1 - Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose
AU - Tsuzuki, T.
AU - Takano, S.
AU - Sakaguchi, N.
AU - Kudoh, T
AU - Murayama, Takashi
AU - Sakurai, Takashi
AU - Higashida, Haruhiro
AU - Weber, K
AU - Guse, A H
AU - Kameda, T.
AU - Hirokawa, T.
AU - Kumaki, Y.
AU - Arisawa, M
AU - Potter, Barry
AU - Shuto, Satoshi
PY - 2015/6
Y1 - 2015/6
N2 - 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.
AB - 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.
UR - http://dx.doi.org/10.1166/msr.2014.1035
U2 - 10.1166/msr.2014.1035
DO - 10.1166/msr.2014.1035
M3 - Article
VL - 3
SP - 35
EP - 51
JO - Messenger
JF - Messenger
SN - 2167-955X
IS - 1-2
ER -