biostudies-literatureAndy DMedical College of WisconsinNational Institutes of HealthNational Institute of General Medical SciencesNIGMS NIH HHS117099https://www.ebi.ac.uk/biostudies/studies/S-EPMC9842072biostudies-literatureUnknown76A photo-clickable analog of adenosine was devised and synthesized in which the photoactive functional group (8-azidoadenosine) and the click moiety (2'-O-propargyl-ether) were compactly combined within the structure of the adenosine nucleoside itself. We synthesized 8-N₃-2'-O-propargyl adenosine in four steps starting from adenosine. This photo-clickable adenosine was 5'-phosphorylated and coupled to nicotinamide mononucleotide to form the NAD analog 8-N₃-2'-O-propargyl-NAD. This NAD analog was recognized by Aplysia californica ADP-ribosyl cyclase and enzymatically cyclized producing 8-N₃-2'-O-propargyl cyclic ADP-ribose. Photo-clickable cyclic-ADP-ribose analog was envisioned as a probe to label cyclic ADP-ribose binding proteins. The monofunctional 8-N<suBioorganic & medicinal chemistrySynthesis 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.PMC9842072R01 GM088790R01-GM088790R15-GM131329R15 GM131329Walseth TFGunaratne GSMarchant JSSlama JTAndy DfalseSynthesis 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.A photo-clickable analog of adenosine was devised and synthesized in which the photoactive functional group (8-azidoadenosine) and the click moiety (2'-O-propargyl-ether) were compactly combined within the structure of the adenosine nucleoside itself. We synthesized 8-N₃-2'-O-propargyl adenosine in four steps starting from adenosine. This photo-clickable adenosine was 5'-phosphorylated and coupled to nicotinamide mononucleotide to form the NAD analog 8-N₃-2'-O-propargyl-NAD. This NAD analog was recognized by Aplysia californica ADP-ribosyl cyclase and enzymatically cyclized producing 8-N₃-2'-O-propargyl cyclic ADP-ribose. Photo-clickable cyclic-ADP-ribose analog was envisioned as a probe to label cyclic ADP-ribose binding proteins. The monofunctional 8-N<su2022-01-01T00:00:00Z2022 Dec2025-04-04T03:01:16.662Z2025-04-04T03:01:16.662ZS-EPMC98420723644627110.1016/j.bmc.2022.117099