Design and synthesis of 4″,6″-unsaturated cyclic ADP-carbocyclic-ribose, a Ca²⁺-mobilizing agent selectively active in T cells

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• 作者：Takashi Kudoh ; Takashi Murayama ; Minako Hashii ; Haruhiro Higashida ; Takashi Sakurai ; Clarisse Maechling ; Bernard Spiess ; Karin Weber ; Andreas H. Guse ; Barry V.L. Potter ; Mitsuhiro Arisawa ; Akira Matsu
• 刊名：Tetrahedron
• 出版年：2008
• 出版时间：6 October 2008
• 年：2008
• 卷：64
• 期：41
• 页码：9754-9765
• 全文大小：884 K

文摘

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.