Bioorganic chemistry of cyclic ADP-ribose (cADPR)

The objective of this brief review is to present an overview of the bioorga nic chemistry of cyclic-ADP-ribose (cADPR) with special emphasis on the met hodology used for the synthesis of analogues of cADPR. New structural analo gues of cADPR can be prepared using either the biomimetic method or ADP-rib osyl cyclase from Aplysia californica. For the most part, both procedures g ive similar product profiles, but higher yields are generally obtained with the enzymatic method. These synthetic methodologies have allowed the trans formation of a variety of structurally modified analogues of NAD(+) into th eir corresponding cyclic nucleotides. Several of these novel analogues are more potent than cADPR in inducing calcium release and are also more stable towards degradative enzymes. They could serve as valuable affinity probes for the isolation of cADPR-binding proteins. (C) 1999 Elsevier Science Ltd. All rights reserved.