Title of article :
Design and synthesis of 4″,6″-unsaturated cyclic ADP-carbocyclic-ribose, a Ca2+-mobilizing agent selectively active in T cells
Author/Authors :
Takashi Kudoh، نويسنده , , Takashi Murayama، نويسنده , , Minako Hashii، نويسنده , , Haruhiro Higashida، نويسنده , , Takashi Sakurai، نويسنده , , Clarisse Maechling، نويسنده , , Bernard Spiess، نويسنده , , Karin Weber، نويسنده , , Andreas H. Guse، نويسنده , , Barry VL Potter، نويسنده , , Mitsuhiro Arisawa، نويسنده , , Akira Matsuda and Fuyuhiko Inagaki، نويسنده , , Satoshi Shuto، نويسنده ,
Abstract :
We previously developed cyclic ADP-carbocyclic-ribose (cADPcR, 3a) as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger. The unsaturated carbocyclic-ribose analogs of cADPR, i.e., 4″,6″-didehydro-cADPcR (8a) and its inosine congener 4″,6″-didehydro-cIDPcR (8b) were newly designed and successfully synthesized using the key intramolecular condensation reaction with S-phenyl phosphorothioate-type substrates. The Ca2+-mobilizing potency of the compounds was examined in sea urchin egg homogenates, NG108-15 neuronal cells, and permeabilized Jurkat T-lymphocytes, which may indicate that 4″,6″-didehydro-cADPcR is the first cADPR analog selectively active in T cells. Acid–base behavior and conformation of 8a were also investigated and compared with those of cADPcR.
