N-[9-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxyoxolan-2-yl]-6-oxo-1H-purin-2-yl]acetamide | 944138-03-8

• 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: N-[9-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxyoxolan-2-yl]-6-oxo-1H-purin-2-yl]acetamide
• CAS: 944138-03-8
• 化学式: C₄₈H₆₄N₇O₉PSi
• 分子量: 942.137
• InChiKey: DGDYJRDKFZTURB-CAOYMVPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.05
• 重原子数：
  66.0
• 可旋转键数：
  20.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  184.31
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  N-[9-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxyoxolan-2-yl]-6-oxo-1H-purin-2-yl]acetamide 、 3-羟基丙腈 在 1H-imidazole perchlorate 、 苯基二硫化物 作用下， 以 乙腈 为溶剂， 反应 7.25h， 生成
  参考文献：
  名称：

  Conservative Change to the Phosphate Moiety of Cyclic Diguanylic Monophosphate Remarkably Affects Its Polymorphism and Ability To Bind DGC, PDE, and PilZ Proteins

  摘要：

  The cyclic dinucleotide c-di-GMP is a master regulator of bacterial virulence and biofilm formation. The activations of c-di-GMP metabolism proteins, diguanylate cyclases (DGCs) and phosophodiesterases (PDEs), usually lead to diametrically opposite phenotypes in bacteria. Analogues of c-di-GMP, which can selectively modulate the activities of c-di-GMP processing proteins, will be useful chemical tools for studying and altering bacterial behavior. Herein we report that a conservative modification of one of the phosphate groups in c-di-GMP with a bridging sulfur in the phosphodiester linkage affords an analogue called endo-S-c-di-GMP. Computational, NMR (including DOSY), and CD experiments all reveal that, unlike c-di-GMP, endo-S-c-di-GMP does not readily form higher aggregates. The lower propensity of endo-S-c-di-GMP to form aggregates (as compared to that of c-di-GMP) is probably due to a higher activation barrier to convert from the "open" conformer (where the two guanines are on opposite faces) to the "closed" conformer (where the two guanines are on the same face). Consequently, endo-S-c-di-GMP has selectivity for proteins that bind monomeric but not dimeric c-di-GMP, which form from the "closed" conformer. For example, endo-S-c-di-GMP can inhibit the hydrolysis of c-di-GMP by RocR (a PDE enzyme that binds monomeric c-di-GMP) but did not bind to A1g44 (a PilZ protein) or regulate WspR (a DGC enzyme that has been shown to bind to dimeric c-di-GMP). This work demonstrates that selective binding to different classes of c-di-GMP binding proteins could be achieved by altering analogue conformer populations (conformational steering). We provide important design principles for the preparation of selective PDE inhibitors and reveal the role played by the c-di-GMP backbone in c-di-GMP polymorphism and binding to processing proteins.

  DOI：

  10.1021/ja1112029

文献信息

• Construction of photoresponsive RNA for photoswitching RNA hybridization
  作者：Hiroshi Ito、Xingguo Liang、Hidenori Nishioka、Hiroyuki Asanuma

  DOI：10.1039/c0ob00432d

  日期：——

  By introducing azobenzenes into RNA using D-threoninol as a scaffold, a photoresponsive RNA was constructed for efficiently photoswitching the formation and dissociation of RNA/RNA duplexes. The difference in melting temperature (Tm) between the trans and cis forms was so large that efficient photoregulation of RNA hybridization became possible, irrespective of the sequence adjacent to the introduced azobenzene. Compared to the corresponding photoresponsive DNA, the photoregulatory efficiency of azobenzene-modified RNA was even higher due to the drastic destabilization by cis-azobenzene. Structural analysis by NMR and molecular modeling indicated that the planar trans-azobenzene could not stabilize the RNA/RNA duplex with a rigid A-form structure by base pair stacking. However, the large steric hindrance caused by nonplanar cis-azobenzene was quite effective at distorting and destabilizing the duplex structure. We also discuss the effect of methylation of azobenzene at the ortho positions on photoregulation of RNA/RNA duplex formation. This newly constructed photoresponsive RNA has promising applications such as photoswitching of RNA functions.

  通过以 D-苏氨醇为支架将偶氮苯引入 RNA，构建了一种具有光致伸缩性的 RNA，可有效地对 RNA/RNA 双链的形成和解离进行光开关。反式和顺式的熔化温度（Tm）相差很大，因此可以对 RNA 杂交进行有效的光调节，而与引入的偶氮苯相邻的序列无关。与相应的光致反应 DNA 相比，偶氮苯修饰的 RNA 的光致调节效率更高，因为顺式偶氮苯会使其稳定性急剧下降。核磁共振和分子模型的结构分析表明，平面反式偶氮苯无法通过碱基对堆叠稳定具有刚性 A 型结构的 RNA/RNA 双链。然而，非平面顺式偶氮苯造成的巨大立体阻碍却能有效地扭曲和破坏双链结构的稳定性。我们还讨论了偶氮苯在正交位置的甲基化对 RNA/RNA 双链形成的光调节作用。这种新构建的具有光致伸缩性的 RNA 具有广阔的应用前景，例如 RNA 功能的光开关。
• Ion-tagged synthesis of an oligoribonucleotide pentamer — The continuing versatility of TBDMS chemistry
  作者：Robert A Donga、Tak-Hang Chan、Masad J Damha

  DOI：10.1139/v07-022

  日期：2007.4.1

  An oligoribonucleotide has been synthesized in solution, using an ionic-liquid-based soluble tag at a scale several hundred times that of a standard solid-phase synthesis approach. Ogilvie's 2′-TBDMS strategy was adopted, and because of the resultant increase in lipophilicity, it allowed an easier purification of the growing oligomer compared with the previously observed for DNA, which does not require 2′ protection. The procedure is illustrated by the synthesis of the pentaribonucleotide sequence AGAUC, corresponding to a segment of the tRNA^fMet from E. coli.Key words: solution-phase RNA synthesis, ionic-liquid tag.

  利用离子液体可溶性标签在溶液中合成了一种寡核苷酸，其规模是标准固相合成方法的几百倍。该方法采用了 Ogilvie 的 2′-TBDMS 策略，由于亲油性增加，与以前观察到的不需要 2′ 保护的 DNA 相比，更容易纯化生长中的寡聚体。该过程以五位核苷酸序列 AGAUC 的合成为例进行说明，该序列与大肠杆菌 tRNAfMet 的一个片段相对应。