Synthesis of cyclic adenosine 5′-diphosphate ribose analogues: a C2′ endo/syn "southern" ribose conformation underlies activity at the sea urchin cADPR receptorThis paper is part of an Organic & Biomolecular Chemistry web theme issue on chemical biology

Novel 8-substituted base and sugar-modified analogues of the Ca 2+ mobilizing second messenger cyclic adenosine 5′-diphosphate ribose (cADPR) were synthesized using a chemoenzymatic approach and evaluated for activity in sea urchin egg homogenate (SUH) and in Jurkat T-lymphocytes; conformational analysis investigated by 1 H NMR spectroscopy revealed that a C2′ endo / syn conformation of the "southern" ribose is crucial for agonist or antagonist activity at the SUH-, but not at the T cell-cADPR receptor. Conformational analysis of cyclic ADP-ribose analogues reveals a correlation between a C2′ endo / syn "southern" ribose conformation and activity in sea urchin egg homogenates.