2-phospho-cyclic ADP-ribose

Jacobson, M. K Coyle, D, L-, Vu, C- Q Kim, H-, and Jacobson, E. L. (1W7). Preparation of cyclic ADP-ribose, 2 -phospho-cyclic ADP-ribose, and nicotinate adenine dinucleotide phosphate Possible second messengers of calcium signaling. Methods Enziftao . 280, Part J, 265-275. 

Nucleoside Cyclic Phosphates. - Two novel fluorescent analogues of the secondary messenger molecule cyclic ADP-ribose (cADPR) have been pre-pared. Reaction of e-NAD (73) with sodium bromide in DMF in the presence of triethylamine gave the 9-cyclic ADP-ribose 74 whilst the enzyme catalysed cyclisation using Aplysia californica gives the N1-alkylated (equivalent to N7 in adenine) product. The novel cyclic etheno-CDP-ribose 75 was obtained by the enzymatic route and by the chemical cyclisation, albeit in poor yield in the latter case. A P NMR characterisation of cyclic ADP-ribose (cADPR) and its 2 -phospho-cyclic ADP-ribose has been published. ... 

Figure 7.5 Adenosine diphosphate (ADP)-ribosylation biochemical reactions. Mono-ADP-ribosyltransferases (ARTs) and poly-ADP-ribose pol5mierases Poly (PARPs) catalyse the ADP-ribose moiety of NAD transfer to amino acid residues. ADP-ribosyl cyclases generate cyclic ADP-ribose and 2-phospho-cyclic ADP-ribose from NAD and NADP, respectively. Both molecules trigger cyclic ADP-ribose cytosolic Ca " elevation, presumably by activating the ryanodine receptor in the endoplasmic/sarcoplasmic reticulum (RER). SIRTl catalyses a reaction that couples protein deacetylation to NAD hydrolysis.

Several uncertainties have complicated our understanding of the role of Ca2+ in signaling. What is the source of Ca2+ How much of it enters cells from the outside and how much is released from internal stores Where are the internal stores What other kinds of ion channels are present and what second messengers regulate them The sarcoplasmic reticulum of skeletal muscle and also membranes in many other cells contain ryanodine receptors as well as InsP3 receptors.282 293 Both of these receptors have similar structures and contain Ca2+ channels. However, the ryanodine receptors are activated by cyclic ADP ribose (cADPR),294/295 which was first discovered as a compound inducing the release of Ca2+ in sea urchin eggs.296 The 2-phospho derivative of cADPR may also have a similar function.297... 

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