S-[2-[[(2R,3R,4R,5R)-5-(6-benzamidopurin-9-yl)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-3-yl]oxy-pyrrolidin-1-ylphosphanyl]sulfanylethyl] benzenecarbothioate | 1374755-65-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: S-[2-[[(2R,3R,4R,5R)-5-(6-benzamidopurin-9-yl)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-3-yl]oxy-pyrrolidin-1-ylphosphanyl]sulfanylethyl] benzenecarbothioate
• CAS: 1374755-65-3
• 化学式: C₅₇H₆₅N₆O₈PS₂Si
• 分子量: 1085.37
• InChiKey: ALJIYXCITZABFP-WOMFGPHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.41
• 重原子数：
  75
• 可旋转键数：
  23
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  199
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  5'-O-（4,4'-二甲氧基三苯甲基）-2'-O-叔丁基二甲基硅基-N6-苯甲酰基腺苷 在 四氮唑 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 S-[2-[[(2R,3R,4R,5R)-5-(6-benzamidopurin-9-yl)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-3-yl]oxy-pyrrolidin-1-ylphosphanyl]sulfanylethyl] benzenecarbothioate
  参考文献：
  名称：

  Gene Silencing Activity of siRNA Molecules Containing Phosphorodithioate Substitutions

  摘要：

  Chemically synthesized small interfering RNAs (siRNAs) have been widely used to identify gene function and hold great potential in providing a new class of therapeutics. Chemical modifications are desired for therapeutic applications to improve siRNA efficacy. Appropriately protected ribonucleoside-3'-yl S-[beta-(benzoylmercapto)-ethyl]pyrrolidino-thiophosphoramidite monomers were prepared for the synthesis of siRNA containing phosphorodithioate (PS2) substitutions in which the two non-bridging oxygen atoms are replaced by sulfur atoms. A series of siRNAs containing PS2 substitutions have been strategically designed, synthesized, and evaluated for their gene silencing activities. These PS2-siRNA duplexes exhibit an A-form helical structure similar to unmodified siRNA. The effect of PS2 substitutions on gene silencing activity is position-dependent, with certain PS2-siRNAs showing activity significantly higher than that of unmodified siRNA. The relative gene silencing activities of siRNAs containing either PS2 or phosphoromonothioate (PS) linkages at identical positions are variable and depend on the sites of modification. 5'-Phosphorylation of PS2-siRNAs has little or no effect on gene silencing activity. Incorporation of PS2 substitutions into siRNA duplexes increases their serum stability. These results offer preliminary evidence of the potential value of PS2-modified siRNAs.

  DOI：

  10.1021/cb300078e

文献信息

• Gene Silencing Activity of siRNA Molecules Containing Phosphorodithioate Substitutions
  作者：Xianbin Yang、Malgorzata Sierant、Magdalena Janicka、Lukasz Peczek、Carlos Martinez、Tom Hassell、Na Li、Xin Li、Tianzhi Wang、Barbara Nawrot

  DOI：10.1021/cb300078e

  日期：2012.7.20

  Chemically synthesized small interfering RNAs (siRNAs) have been widely used to identify gene function and hold great potential in providing a new class of therapeutics. Chemical modifications are desired for therapeutic applications to improve siRNA efficacy. Appropriately protected ribonucleoside-3'-yl S-[beta-(benzoylmercapto)-ethyl]pyrrolidino-thiophosphoramidite monomers were prepared for the synthesis of siRNA containing phosphorodithioate (PS2) substitutions in which the two non-bridging oxygen atoms are replaced by sulfur atoms. A series of siRNAs containing PS2 substitutions have been strategically designed, synthesized, and evaluated for their gene silencing activities. These PS2-siRNA duplexes exhibit an A-form helical structure similar to unmodified siRNA. The effect of PS2 substitutions on gene silencing activity is position-dependent, with certain PS2-siRNAs showing activity significantly higher than that of unmodified siRNA. The relative gene silencing activities of siRNAs containing either PS2 or phosphoromonothioate (PS) linkages at identical positions are variable and depend on the sites of modification. 5'-Phosphorylation of PS2-siRNAs has little or no effect on gene silencing activity. Incorporation of PS2 substitutions into siRNA duplexes increases their serum stability. These results offer preliminary evidence of the potential value of PS2-modified siRNAs.