8-methyl-2',3',5'-tris-tert-butyldimethylsilylinosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 8-methyl-2',3',5'-tris-tert-butyldimethylsilylinosine
• 英文别名: 9-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-8-methyl-1H-purin-6-one
• 化学式: C₂₉H₅₆N₄O₅Si₃
• 分子量: 625.044
• InChiKey: MIFFAXFXCVKMPK-HUBRGWSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.13
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  96.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-methyl-2',3',5'-tris-tert-butyldimethylsilylinosine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以97%的产率得到8-methylinosine
  参考文献：
  名称：

  Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from Aplysia californica:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes

  摘要：

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.

  DOI：

  10.1021/jm060275a
• 作为产物：
  描述：

  8-iodo-2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine 、 四甲基锡 在 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以96%的产率得到8-methyl-2',3',5'-tris-tert-butyldimethylsilylinosine
  参考文献：
  名称：

  Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from Aplysia californica:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes

  摘要：

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.

  DOI：

  10.1021/jm060275a

文献信息

• Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from <i>Aplysia </i><i>californica</i>:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes
  作者：Christelle Moreau、Gerd K. Wagner、Karin Weber、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm060275a

  日期：2006.8.1

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.