Substitution at the 8-position of 3''-deoxy-cyclic ADP-carbocyclic-ribose, a highly potent Ca2+-mobilizing agent, provides partial agonists.

ABSTRACT

We previously showed that 3''-deoxy-cyclic ADP-carbocyclic-ribose (3''-deoxy-cADPcR, 4) is a stable and highly potent analogue of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. From these results, we designed and synthesized other 3''-modified analogues of cADPcR having a substituent at the 8-position and found that this modification at the 8-position made them partial agonists. Among these compounds, 8-NH(2)-3''-deoxy-cADPcR (10) was identified as a potent partial agonist with an EC(50) value of 17 nM.