Synthesis and biological evaluation of novel photo-clickable adenosine and cyclic ADP-ribose analogs: 8-N3-2′-O-propargyladenosine and 8-N3-2′-O-propargyl-cADPR

•The photoactive and clickable adenosine analog, 8-N3-2ʹ-O-propargyladenosine was synthesized from 8-bromoadenosine in three steps.•Photo-clickable adenosine is a useful new scaffold for chemical probes to identify proteins which interact with a variety of adenosine nucleosides and nucleotides.•8-N3-2ʹ-O-propargyladenosine was converted to its NAD derivative, and enzymatically cyclized using Aplasia californica ADP-ribosyl cyclase. The result was a photoactive and clickable analog of the second messenger cyclic ADP-ribose.•Combining 8‑adenosyl and 2ʹ-O-ribosyl substituents into a cyclic ADP-ribose analog was shown to result in a significant decrease in agonist potency when compared to the potency of the two singly substituted analogs.