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Structure-activity relationship of cyclic ADP-ribose, an update

Andreas H. Guse*   

  1. The Calcium Signalling Group, Department of Biochemistry and Signal Transduction, and Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany

  • Received:2013-02-16 Revised:2013-02-28 Online:2013-03-18 Published:2013-03-18
  • Contact: Andreas H. Guse

Abstract:

Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.

Key words: Cyclic ADP-ribose, Calcium signaling, Cyclic ADP-ribose analogue, Ryanodine receptor, TRPM2, Cellular signal transduction

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