thymidine 5'-phosphorothioate | 15548-51-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: thymidine 5'-phosphorothioate
• 英文别名: thymidyl 5'-phosphorothioate；thymidine-5'-thiophosphate；Thymidin-5'-thionophosphat；Thymidin-5'-phosphorothioat；P-thio-[5']thymidylic acid；Thymidin-5'-phosphorthionsaeure；Thymidin 5'-O-phosphorothioat；1-[(2R,4S,5R)-5-(dihydroxyphosphinothioyloxymethyl)-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 15548-51-3
• 化学式: C₁₀H₁₅N₂O₇PS
• 分子量: 338.278
• InChiKey: OJRKJKYGUAALCJ-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  thymidine 5'-phosphorothioate 、 7-Amino-N-(2-ethylaminocarbonyliodomethyl)-4-methylcoumarin 生成 S-<-2-<-(-4-methyl-2-oxo-2-H-chromen-7-yl)-amino>-ethylaminocarbonylmethyl>-deoxythymidine-5'-phosphorothioate
  参考文献：
  名称：

  A DFDL UV picosecond fluorescence spectrometer: Application to aqueous solutions of peptides and nucleotide dye conjugates

  摘要：

  AbstractUsing a new type of fluorescence lifetime spectrometer, the time resolution of single shot fluorescence detection is improved by two orders of magnitude. The spectrometer is based on a streak camera and an excimer laser pumped distributed feedback dye laser (DFDL) providing UV pulses of 50 μJ and 15 ps FWHM, corresponding to a peak power of ∼ 5 · 106 W in the ultraviolet. —This spectrometer is used to investigate the fluorescence decay of peptides containing a tyrosine as the single fluorophore. Peptides with tyrosine at the N‐terminus reveal a biexponential decay, while peptides with C‐terminal tyrosine are mainly monoexponential. This difference can be explained by the relative orientation of the fluorescing phenol ring and the quenching peptide bond. —The fluorescence decay of a number of peptides with tyrosine in a non terminal position can be described by two lifetimes, 2.3 · 0.1 ns and 380 ± 70 ps, where the percentage of the long lifetime increases to up to 100% when the rotational flexibility of the peptide chain decreases, either due to increasing weight of the chain or due to formation of an H‐bridge. —Similar processes seem to be relevant for the fluorescence of the dye coumarin 120 coupled to nucleotides. The fluorescence lifetime of such molecules is significantly different, so that the four DNA nucleotides can be identified on the basis of the fluorescence decay of the attached dye.

  DOI：

  10.1002/bbpc.19890930324
• 作为产物：
  描述：

  RP-thymidylyl-3',5'-thymidine phosphoromonothiolate 在 phosphodiesterase(E_.⁽¹⁾C₃₄₁) 作用下， 生成 thymidine 5'-phosphorothioate
  参考文献：
  名称：

  The chemical synthesis of the RP and SP diastereomers of thymidyl(3′-5′)thymidyl 0,0-phosphorothioate

  摘要：

  DOI：

  10.1016/s0040-4039(00)88727-4

文献信息

• SILENCING OF POLO-LIKE KINASE EXPRESSION USING INTERFERING RNA
  申请人：PROTIVA BIOTHERAPEUTICS, INC.

  公开号：US20160115483A1

  公开（公告）日：2016-04-28

  The present invention provides compositions comprising interfering RNA (e.g., siRNA, aiRNA, miRNA) that target polo-like kinase 1 (PLK-1) expression and methods of using such compositions to silence PLK-1 expression. More particularly, the present invention provides unmodified and chemically modified interfering RNA molecules which silence PLK-1 expression and methods of use thereof. The present invention also provides serum-stable nucleic acid-lipid particles (e.g., SNALP) comprising an interfering RNA molecule described herein, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing PLK-1 gene expression by administering an interfering RNA molecule described herein to a mammalian subject. The present invention additionally provides methods of identifying and/or modifying PLK-1 interfering RNA having immunostimulatory properties. Methods for sensitizing a cell such as a cancer cell to the effects of a chemotherapy drug comprising sequentially delivering PLK-1 interfering RNA followed by the chemotherapy drug are also provided.

  本发明提供了包含干扰RNA（例如siRNA、aiRNA、miRNA）的组合物，其靶向波洛样激酶1（PLK-1）表达，并提供了使用这种组合物来沉默PLK-1表达的方法。更具体地说，本发明提供了未修饰和化学修饰的干扰RNA分子，这些分子可以沉默PLK-1表达，并提供了它们的使用方法。本发明还提供了含有干扰RNA分子、阳离子脂质和非阳离子脂质的血清稳定核酸-脂质颗粒（例如SNALP），这些颗粒还可以进一步包含抑制颗粒聚集的共轭脂质。本发明还提供了通过向哺乳动物主体施用本文描述的干扰RNA分子来沉默PLK-1基因表达的方法。本发明还提供了识别和/或修改具有免疫刺激性能的PLK-1干扰RNA的方法。此外，还提供了一种通过顺序输送PLK-1干扰RNA后接着化疗药物来使细胞（如癌细胞）对化疗药物产生敏感性的方法。
• 2'-deoxyribonucleoside 3'-aryl phosphoranilidates
  作者：Z.J. Leśnikowski、W. Niewiarowski、W.S. Zieliński、W.J. Stec

  DOI：10.1016/0040-4020(84)85099-1

  日期：1984.1

  Phosphorylation of the 5'-O-monomethoxytrityl-2'-deoxyribonucleosides by means of aryl phosphoranilidochloridates gives the diastereoisomers of 5'-O-monomethoxytrityl-2'-deoxyribonucleoside 3'-aryl phosphoranilidates. Their separation can be performed by means of chromatographic techniques. They can be further converted to the 2'-deoxyribonucleoside cyclic 3'-5' phosphoranilidates, which are intermediates

  5'-O-单甲氧基三苯甲基-2'-脱氧核糖核苷的磷酸化借助于芳基磷酰二氯氯酸酯得到5'-O-单甲氧基三苯甲基-2'-脱氧核糖核苷3'-芳基磷酸苯二酸酯的非对映异构体。它们的分离可以通过色谱技术来进行。它们可以进一步转化为2'-脱氧核糖核苷环状的3'-5'磷酸苯胺酸酯，它们是在磷处具有已知绝对构型的2'-脱氧核糖核苷环状（3'-5'）硫代磷酸酯的立体有择合成的中间体。
• An Efficient Reagent for the Phosphorylation of Deoxyribonucleosides, DNA Oligonucleotides, and Their Thermolytic Analogues
  作者：Cristina Ausín、Andrzej Grajkowski、Jacek Cieślak、Serge L. Beaucage

  DOI：10.1021/ol0516263

  日期：2005.9.1

  and demonstrated efficiency in the synthesis of conventional 5'-/3'-phosphate/thiophosphate monoester derivatives of 2'-deoxyribonucleosides and DNA oligonucleotides. Moreover, the use of 11 has enabled the preparation of the dinucleoside phosphorothioate analogue 26 in high yields (>95%) with minimal cleavage (<2%) of the thermolytic thiophosphate protecting group.

  [反应：见正文]从2巯基乙酸甲酯分三步制备亚磷酰胺11，并证明了2'-脱氧核糖核苷的常规5'-/ 3'-磷酸酯/硫代磷酸酯单酯衍生物和DNA寡核苷酸的合成效率。而且，使用11使得能够以高收率（＞ 95％）制备二核苷硫代磷酸酯类似物26，而热解硫代磷酸酯保护基团的裂解最小（＜2％）。
• Method and compounds for solid phase synthesis of oligonucleotides and oligonucleotide analogs
  申请人：POLISH ACADEMY OF SCIENCES, Center of Molecular and Macromolecular Studies

  公开号：EP0506242A1

  公开（公告）日：1992-09-30

  Methods and compounds are provided for solid phase synthesis of oligonucleotides and related polymers by condensing protected monomer-O-[1,3,2-dichalcogen-substituted-phospholane] synthons in the presence of a catalytic base. Compounds of the invention include 2-N-substituted- 1,3,2-dichalcogen-substituted-phospholane precursors of the above synthons, the protected monomer-O-[1,3,2-dichalcogen-substituted-phospholane] synthons, and P-chiral oligonucleotides and related P-chiral polymers.

  本发明提供了在催化碱存在下通过缩合受保护单体-O-[1,3,2-二钙化原-取代-磷脂烷]合成物固相合成寡核苷酸和相关聚合物的方法和化合物。本发明的化合物包括上述合成物的 2-N-取代-1,3,2-二钙化原-取代-磷杂环戊烷前体、受保护单体-O-[1,3,2-二钙化原-取代-磷杂环戊烷]合成物以及 P 手性寡核苷酸和相关 P 手性聚合物。
• CROSS-LINKED NUCLEOSIDE AND NUCLEOTIDE USING SAME
  申请人：OSAKA UNIVERSITY

  公开号：EP4108262A1

  公开（公告）日：2022-12-28

  A cross-linked nucleoside of the present invention is a compound represented by the formula (I) below. The cross-linked nucleoside of the present invention is usable as a substitute for a phosphorothioate-modified nucleic acid, which has a risk of, for example, accumulation in a specific organ. The cross-linked nucleoside also has excellent industrial productivity.

  本发明的交联核苷是由下式(I)表示的化合物。本发明的交联核苷可用作硫代磷酸修饰核酸的替代品，硫代磷酸修饰核酸有在特定器官中蓄积的风险。交联核苷还具有出色的工业生产力。