title: Design, Synthesis, and Identification of 4″α-Azidoethyl-cyclic ADP-Carbocyclic-ribose as a Highly Potent Analogue of Cyclic ADP-Ribose, a Ca(2+)-Mobilizing Second Messenger.
abstract: Cyclic adenosine diphosphate-carbocyclic-ribose (cADPcR, 2) is a stable equivalent of cyclic adenosine diphosphate-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. On the basis of the structure-activity relationship of cADPR-related compounds and three-dimensional structural modeling of cADPcR, we designed and synthesized cyclic-ADP-4″α-azidoethyl carbocyclic-ribose (N3-cADPcR, 3) to demonstrate that it has a highly potent Ca(2+)-mobilizing activity (EC50 = 24 nM). N3-cADPcR will be a useful precursor for the preparation of biological tools effective to investigate cADPR-mediated signaling pathways.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tsuzuki
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takano
authors.affiliation: Department of Pharmacology, Juntendo University School of Medicine , 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 , Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST) , 2-4-7 Aomi, Koutou-ku, Tokyo 135-0064, Japan.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Kameda
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Fukuda
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Arisawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.|Center for Research and Education on Drug Discovery, Hokkaido University , Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shuto
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008968:Molecular Conformation; D015290:Second Messenger Systems / Q000187:drug effects*
chemical_list: C439996:cyclic ADP-carbocyclic-ribose; D036563:Cyclic ADP-Ribose; D002118:Calcium