(pT)5 | 39014-21-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (pT)5
• 英文别名: (dT)5；5'-Ttttt-3'P；[(2R,3S,5R)-2-[[hydroxy-[(2R,3S,5R)-2-[[hydroxy-[(2R,3S,5R)-2-[[hydroxy-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] [(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-3-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate
• CAS: 39014-21-6
• 化学式: C₅₀H₆₇N₁₀O₃₆P₅
• 分子量: 1539.0
• InChiKey: CNKIAEDEMAZRJE-OPOFJALESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -9
• 重原子数：
  101
• 可旋转键数：
  28
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  603
• 氢给体数：
  12
• 氢受体数：
  36

反应信息

• 作为反应物：
  描述：

  (pT)5 、 N⁶-benzoyl-5'-O-(monomethoxytrityl)adenosine 2',3'-bis-O-(β-cyanoethyl N,N-diisopropylphosphoramidite) 生成
  参考文献：
  名称：

  分支寡核苷酸的自动化固相合成

  摘要：

  已经开发了合成支链RNA和DNA寡核苷酸的通用程序。合成策略涉及在DNA或RNA寡聚物的3'-> 5'合成中，使用自动DNA合成仪在固相，受控孔玻璃载体上进行合成。通过将两个相邻的聚合物结合的核苷酸链与四唑活化的腺苷2'，3'-双亚磷酰胺衍生物偶联来引入分支点核苷。

  DOI：

  10.1016/s0040-4039(01)93876-6
• 作为产物：
  描述：

  5-O-(4,4-二甲氧基三苯基甲基)-胸苷-3-O-丁二酸 生成 (pT)5
  参考文献：
  名称：

  摘要：

  A simple protocol based on Polymerization reactions has been developed for the preparation of high-loading polymer supports. useful for large-scale synthesis of oligonucleotides. Polymer supports of different pore sizes have been employed in the present investigation to improve the functional-group density on them. A ten-to twelvefold increase in the loading of the functional groups, after the polymerization reaction. has been observed. The support was then used in the subsequent reaction to attach the leader nucleoside to obtain fully functionalized supports 6a-6c by oligonucleotide synthesis in an automated DNA synthesizer. The amino-alkylated-supports 5a-5c were directly employed for the synthesis of oligonucleotide 3'-phosphates. The oligonucleotides and oligonucleotide 3'-phosphates synthesized on these supports were compared with the corresponding standard oligomers with respect to their retention time on HPLC. These were further characterized on MALDI-TOF mass spectrometry.

  DOI：

  10.1002/1522-2675(200209)85:9<2754::aid-hlca2754>3.0.co;2-n

文献信息

• Solid Phase Synthesis of Oligonucleotides Bearing Phosphate and Thiophosphate at Their 3′-Termini
  作者：P. Kumar、K. C. Gupta、R. Rösch、H. Seliger

  DOI：10.1246/cl.1997.1231

  日期：1997.12

  Controlled pore glass (CPG) containing mercaptoalkyl groups allows the synthesis of oligonucleotides bearing 3′-phosphate or thiophosphate function during final deprotection.

  含有巯基烷基的受控孔隙玻璃（CPG）可在最终脱保护过程中合成带有3′-磷酸或硫磷酸官能团的寡核苷酸。
• 5'‐<i>O</i>‐(2‐Isopropoxyprop‐2‐yl)‐protected Phosphoramidite Building Blocks in the Liquid Phase Oligonucleotide Synthesis
  作者：Zehong Liang、Petja Rosenqvist、Ella Pajuniemi、Mikko Ora、Petri Heinonen、Pasi Virta、Mikko Oivanen

  DOI：10.1002/ejoc.202300614

  日期：2023.9.21

  Liquid phase oligonucleotide synthesis calls for improved methodologies. We have tested an acetal modification for protection of the 5’-O site of nucleotide building blocks. Good yields were obtained in synthesis of short 2’-deoxyoligonucleotides by phosphoramidite chemistry on a soluble support. The advantages of the title group include fast cleavage, easily removable volatile residues, and small

  液相寡核苷酸合成需要改进的方法。我们已经测试了用于保护核苷酸构件的5'- O位点的缩醛修饰。在可溶性载体上通过亚磷酰胺化学合成短2'-脱氧寡核苷酸，获得了良好的产率。该标题基团的优点包括快速裂解、易于去除挥发性残留物以及尺寸小，提高了原子经济性。
• Prodrug‐Type Phosphotriester Oligonucleotides with Linear Disulfide Promoieties Responsive to Reducing Environment
  作者：Norihito Sugimoto、Junsuke Hayashi、Ryohei Funaki、Shun‐ichi Wada、Fumito Wada、Mariko Harada‐Shiba、Hidehito Urata

  DOI：10.1002/cbic.202300526

  日期：2023.12.14

  Various chemical modifications have been developed to create new antisense oligonucleotides (AONs) for clinical applications. Our previously designed prodrug‐type phosphotriester‐modified oligonucleotide with cyclic disulfides (cyclic SS PTE ON) can be converted into unmodified ON in an intracellular‐mimetic reducing environment. However, the conversion rate of the cyclic SS PTE ON was very low, and the AON with cyclic SS PTE modifications showed much weaker antisense activity than corresponding to the fully phosphorothioate‐modified AON. In this study, we synthesized several types of PTE ONs containing linear disulfides (linear SS PTE ONs) and evaluated their conversion rates under reducing conditions. From the results, the structural requirements for the conversion of the synthesized linear SS PTE ONs were elucidated. Linear SS PTE ON with promising promoieties showed a nuclease resistance up to 4.8‐fold compared to unmodified ON and a cellular uptake by endocytosis without any transfection reagent. In addition, although the knockdown activity of the linear SS PTE gapmer AON is weaker than that of the fully phosphorothioate‐modified gapmer AON, the knockdown activity is slightly stronger than that of the cyclic SS PTE gapmer AON. These results suggest that the conversion rates may be related to the expression of the antisense activity.

  摘要 人们开发了各种化学修饰方法，以创造新的反义寡核苷酸（AONs）用于临床应用。我们之前设计的原药型磷酸三酯修饰的环状二硫寡核苷酸（环状 SS PTE ON）可在细胞内模拟还原环境中转化为未修饰的 ON。然而，环状 SS PTE ON 的转化率非常低，而且与完全硫代磷酸酯修饰的 AON 相比，环状 SS PTE 修饰的 AON 的反义活性要弱得多。本研究合成了几种含有线性二硫化物的 PTE ON（线性 SS PTE ON），并评估了它们在还原条件下的转化率。研究结果阐明了合成的线性 SS PTE ONs 转化率的结构要求。与未修饰的线性 SS PTE ONs 相比，具有良好前景的线性 SS PTE ONs 显示出高达 4.8 倍的核酸酶抗性，并且无需任何转染试剂即可通过内吞作用被细胞吸收。此外，虽然线性 SS PTE 间隙聚合物 AON 的基因敲除活性弱于完全硫代磷酸酯修饰的间隙聚合物 AON，但其基因敲除活性略强于环状 SS PTE 间隙聚合物 AON。这些结果表明，转化率可能与反义活性的表达有关。
• ——
  作者：Romila Manchanda、Sunil K. Agarwal、Pradeep Kumar、Ashwani K. Sharma、Kailash C. Gupta、Ramesh Chandra

  DOI：10.1002/1522-2675(200209)85:9<2754::aid-hlca2754>3.0.co;2-n

  日期：2002.9

  A simple protocol based on Polymerization reactions has been developed for the preparation of high-loading polymer supports. useful for large-scale synthesis of oligonucleotides. Polymer supports of different pore sizes have been employed in the present investigation to improve the functional-group density on them. A ten-to twelvefold increase in the loading of the functional groups, after the polymerization reaction. has been observed. The support was then used in the subsequent reaction to attach the leader nucleoside to obtain fully functionalized supports 6a-6c by oligonucleotide synthesis in an automated DNA synthesizer. The amino-alkylated-supports 5a-5c were directly employed for the synthesis of oligonucleotide 3'-phosphates. The oligonucleotides and oligonucleotide 3'-phosphates synthesized on these supports were compared with the corresponding standard oligomers with respect to their retention time on HPLC. These were further characterized on MALDI-TOF mass spectrometry.
• Automated solid-phase synthesis of branched oligonucleotides
  作者：Masad J. Damha、Steve Zabarylo

  DOI：10.1016/s0040-4039(01)93876-6

  日期：1989.1

  A general procedure for the synthesis of branched RNA and DNA oligonucleotides has been developed. The synthetic strategy involves the 3′->5′ synthesis of a DNA or RNA oligomer on a solid-phase, controlled-pore glass support with an automated DNA synthesizer. The branch point nucleoside is introduced by coupling of two adjacent polymer bound nucleotide chains with a tetrazole-activated adenosine 2′

  已经开发了合成支链RNA和DNA寡核苷酸的通用程序。合成策略涉及在DNA或RNA寡聚物的3'-> 5'合成中，使用自动DNA合成仪在固相，受控孔玻璃载体上进行合成。通过将两个相邻的聚合物结合的核苷酸链与四唑活化的腺苷2'，3'-双亚磷酰胺衍生物偶联来引入分支点核苷。