title: Synthesis and calcium mobilization activity of cADPR analogues which integrate nucleobase, northern and southern ribose modifications.
abstract: Novel cADPR mimics, which integrate nucleobase, northern and southern ribose modifications were synthesized. The key steps of the synthesis were a Cu(I)-catalyzed Hüisgen [3+2] cycloaddition and a microwave-assisted intramolecular pyrophosphorylation. Preliminary biological investigations showed that these cADPR mimics are membrane-permeating agonists of the calcium signaling pathway. The introduction of chlorine or fluorine at the 2'-position of the southern riboses led to a decrease of activity. The existence of a hydrophobic group on the 3'-OH of the southern riboses does not obviously alter the agonistic activity.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.forename: Peilin
authors.initials: P
authors.lastname: Yu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Yang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yue
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular
chemical_list: D036563:Cyclic ADP-Ribose; D002118:Calcium