title: Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose.
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 derivative8and the 4-thioribosylamine7via equilibrium in7between 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tsuzuki
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takano
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudoh
authors.affiliation: Department of Pharmacology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murayama
authors.affiliation: Department of Pharmacology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Biophysical Genetics, Takaramachi, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Hashii
authors.affiliation: Department of Biophysical Genetics, Takaramachi, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Higashida
authors.affiliation: The Calcium Signalling Group, University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Department of Biochemistry and Signal Transduction, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Weber
authors.affiliation: The Calcium Signalling Group, University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Department of Biochemistry and Signal Transduction, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Guse
authors.affiliation: Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Aomi, Koutou-ku, Tokyo 135-0064, Japan.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Kameda
authors.affiliation: Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Aomi, Koutou-ku, Tokyo 135-0064, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Hirokawa
authors.affiliation: Faculty of Sciences, Hokkaido University, Kita-11, Nishi-8, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kumaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Arisawa
authors.affiliation: Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Barry V L
authors.initials: BV
authors.lastname: Potter
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shuto