5'-O-DMT-2'-O-Me-rA^Pac phosphoramidite | 145520-30-5

• 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: 5'-O-DMT-2'-O-Me-rA^Pac phosphoramidite
• 英文别名: N-[9-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-3-methoxyoxolan-2-yl]purin-6-yl]-2-phenoxyacetamide
• CAS: 145520-30-5
• 化学式: C₄₉H₅₆N₇O₉P
• 分子量: 917.999
• InChiKey: LHJMWCPLFQEOGK-JLZYTDEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  66
• 可旋转键数：
  22
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  174
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  5'-O-DMT-2'-O-Me-rA^Pac phosphoramidite 在 甲胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以82%的产率得到5'-O-dimethoxytritil-2'-O-methyladenosine-3'-O-(2-cianoethyl-N,N-diisopropylphosphoramidite)
  参考文献：
  名称：

  O-Selective Condensation Using P−N Bond Cleavage in RNA Synthesis without Base Protection

  摘要：

  In RNA synthesis without base protection, a new method for O-selective condensation with more than 99% selectivity was developed by 6-nitro-HOBt-mediated cleavage of undesired P(III)-N bonds on nucleobase moieties. Moreover, we for the first time succeeded in synthesizing oligoRNAs without base protection.

  DOI：

  10.1021/ol800911b

文献信息

• [EN] NOVEL MRNA 5'-END CAP ANALOGS, RNA MOLECULE INCORPORATING THE SAME, USES THEREOF AND METHOD OF SYNTHESIZING RNA MOLECULE OR PEPTIDE<br/>[FR] NOUVEAUX ANALOGUES DE COIFFE TERMINALE 5' D'ARNM, MOLÉCULE D'ARN LES INCORPORANT, UTILISATIONS DE CEUX-CI ET PROCÉDÉS DE SYNTHÈSE DE MOLÉCULE D'ARN OU DE PEPTIDE
  申请人：UNIV WARSZAWSKI

  公开号：WO2021162567A1

  公开（公告）日：2021-08-19

  The invention relates to new mRNA 5' end cap analogs, RNA molecules containing them, their uses and methods for their in vitro synthesis, as well as a method for protein or peptide synthesis in vitro or in cell cultures, which method encompases translation of the RNA molecule.

  本发明涉及新的mRNA 5'端帽类似物、含有它们的RNA分子、它们的用途和它们的体外合成方法，以及一种体外或细胞培养中蛋白质或肽的合成方法，该方法包括对RNA分子进行翻译。
• Quick Access to Nucleobase-Modified Phosphoramidites for the Synthesis of Oligoribonucleotides Containing Post-Transcriptional Modifications and Epitranscriptomic Marks
  作者：Kamil Ziemkiewicz、Marcin Warminski、Radoslaw Wojcik、Joanna Kowalska、Jacek Jemielity

  DOI：10.1021/acs.joc.2c01390

  日期：2022.8.5

  nucleobases of commercially available nucleoside phosphoramidites. This method involves the deprotonation of amide groups under phase-transfer conditions and subsequent reaction with electrophilic molecules such as alkyl halides or organic isocyanates. Using this approach, we obtained 10 different classes of modified nucleoside phosphoramidites suitable for the synthesis of oligonucleotides, including several

  在这里，我们报告了一种简单的一步程序，用于修改市售核苷亚磷酰胺的核碱基中的N-亲核基团。该方法涉及在相转移条件下使酰胺基团去质子化，并随后与诸如烷基卤化物或有机异氰酸酯等亲电子分子反应。使用这种方法，我们获得了 10 种不同类型的适合合成寡核苷酸的修饰核苷亚磷酰胺，包括在天然 RNA 或 DNA 中发现的几种非规范核苷酸（例如，m 6 A、i 6 A、m 1 A、g 6 A、m 3 ℃，米4 ℃，米3 U，米1G 和 m 2 G)。核碱基的这种修饰是各种生物体中 RNA 稳定性和翻译活性的转录后调节的常见机制。为了更好地理解这一过程，必须识别和表征相关的细胞识别伙伴（例如蛋白质）。然而，这一步骤受到了对含有此类修饰核苷酸的分子工具的有限访问的阻碍。
• The identity and methylation status of the first transcribed nucleotide in eukaryotic mRNA 5′ cap modulates protein expression in living cells
  作者：Pawel J Sikorski、Marcin Warminski、Dorota Kubacka、Tomasz Ratajczak、Dominika Nowis、Joanna Kowalska、Jacek Jemielity

  DOI：10.1093/nar/gkaa032

  日期：2020.2.28

  7-Methylguanosine 5′ cap on mRNA is necessary for efficient protein expression in vitro and in vivo. Recent studies revealed structural diversity of endogenous mRNA caps, which carry different 5′-terminal nucleotides and additional methylations (2′-O-methylation and m6A). Currently available 5′-capping methods do not address this diversity. We report trinucleotide 5′ cap analogs (m7GpppN(m)pG), which are utilized by RNA polymerase T7 to initiate transcription from templates carrying Φ6.5 promoter and enable production of mRNAs differing in the identity of the first transcribed nucleotide (N = A, m6A, G, C, U) and its methylation status (±2′-O-methylation). HPLC-purified mRNAs carrying these 5′ caps were used to study protein expression in three mammalian cell lines (3T3-L1, HeLa and JAWS II). The highest expression was observed for mRNAs carrying 5′-terminal A/Am and m6Am, whereas the lowest was observed for G and Gm. The mRNAs carrying 2′-O-methyl at the first transcribed nucleotide (cap 1) had significantly higher expression than unmethylated counterparts (cap 0) only in JAWS II dendritic cells. Further experiments indicated that the mRNA expression characteristic does not correlate with affinity for translation initiation factor 4E or in vitro susceptibility to decapping, but instead depends on mRNA purity and the immune state of the cells.

  摘要：在体内和体外高效表达蛋白质需要mRNA上的7-甲基鸟嘌呤5'帽。最近的研究揭示了内源性mRNA帽的结构多样性，它们携带不同的5'-末端核苷酸和额外的甲基化（2'-O-甲基化和m6A）。目前可用的5'-帽方法不能解决这种多样性。我们报告了三核苷酸5'帽类似物（m7GpppN（m）pG），它们被RNA聚合酶T7用于从携带Φ6.5启动子的模板开始转录，并能够产生在第一个转录核苷酸（N = A，m6A，G，C，U）的身份和甲基化状态（±2'-O-甲基化）不同的mRNA。纯化的带有这些5'帽的mRNA被用于研究三种哺乳动物细胞系（3T3-L1，HeLa和JAWS II）中的蛋白质表达。观察到带有5'-末端A / Am和m6Am的mRNA表达最高，而G和Gm的表达最低。带有第一个转录核苷酸（帽1）的2'-O-甲基化mRNA在JAWS II树突状细胞中的表达显著高于未甲基化的对应物（帽0）。进一步的实验表明，mRNA表达特性与翻译起始因子4E的亲和力或体外脱帽易感性无关，而取决于mRNA纯度和细胞的免疫状态。
• Trinucleotide mRNA Cap Analogue <i>N</i>6-Benzylated at the Site of Posttranscriptional ^m6A_m Mark Facilitates mRNA Purification and Confers Superior Translational Properties In Vitro and In Vivo
  作者：Marcin Warminski、Edyta Trepkowska、Miroslaw Smietanski、Pawel J. Sikorski、Marek R. Baranowski、Marcelina Bednarczyk、Hanna Kedzierska、Bartosz Majewski、Adam Mamot、Diana Papiernik、Agnieszka Popielec、Remigiusz A. Serwa、Brittany A. Shimanski、Piotr Sklepkiewicz、Marta Sklucka、Olga Sokolowska、Tomasz Spiewla、Diana Toczydlowska-Socha、Zofia Warminska、Karol Wolosewicz、Joanna Zuberek、Jeffrey S. Mugridge、Dominika Nowis、Jakub Golab、Jacek Jemielity、Joanna Kowalska

  DOI：10.1021/jacs.3c12629

  日期：2024.3.27

  content than reference caps. In some cultured cells, Bn6Am mRNAs provided higher protein yields than mRNAs carrying Am or m6Am, although the effect was cell-line-dependent. m7GpppBn6AmpG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic

  真核 mRNA 通过 7-甲基鸟苷帽进行共转录 5' 端修饰。在高等真核生物中，帽子带有额外的甲基化，例如m6 A m — mRNA 5' 端特有的常见表观转录组标记。这种修饰受到 PCif1 甲基转移酶和 FTO 去甲基化酶的调节，但其生物学功能仍不清楚。在这里，我们设计并合成了m6 A m -cap–m 7 Gppp Bn6 A m pG 的三核苷酸 FTO 抗性N 6-苄基类似物（称为AvantCap ），并使用 T7 聚合酶将其整合到 mRNA 中。与典型的加帽转录本相比，携带Bn6 A m的 mRNA 显示出多种优势。 Bn6 A m部分被证明可作为反相高效液相色谱 (RP-HPLC) 纯化手柄，允许分离加帽和未加帽的 RNA 种类，并产生比参考帽具有更低 dsRNA 含量的转录本。在一些培养的细胞中， Bn6 A m mRNA 比携带 A m或m6 A m 的mRNA 提供更高
• Oligonucleotide Synthesis Involving Deprotection of Amidine-Type Protecting Groups for Nucleobases under Acidic Conditions
  作者：Akihiro Ohkubo、Yasukazu Kuwayama、Yudai Nishino、Hirosuke Tsunoda、Kohji Seio、Mitsuo Sekine

  DOI：10.1021/ol100676j

  日期：2010.6.4

  Amidine-type protecting groups, i.e., N,N-dimethylformamidine (dmf) and N,N-dibutylformamidine (dbf) groups, introduced Into nucleobases were rapidly removed under mild acidic conditions using imidazolium triflate (IMT) or 1-hydroxybenztriazole (HOBt). This new deprotection strategy allowed a 2'-O-methyl-RNA derivative bearing a base-labile group to be efficiently synthesized using a silyl-type linker. It was also found that our new method could be applied to the synthesis of an unmodified RNA oligomer.