3',5'-O-(di-tert-butyl)silyl-2'-O-dimethyl(tert-butyl)silylinosine | 896131-05-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 3',5'-O-(di-tert-butyl)silyl-2'-O-dimethyl(tert-butyl)silylinosine
• 英文别名: 9-[(4aR,6R,7R,7aR)-2,2-Di-tert-butyl-7-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furo[3,2-d][1,3,2]dioxasilin-6-yl]-1,9-dihydro-purin-6-one
• CAS: 896131-05-8
• 化学式: C₂₄H₄₂N₄O₅Si₂
• 分子量: 522.792
• InChiKey: SNODXIXTMOPVEC-QTQZEZTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.28
• 重原子数：
  35.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  100.75
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  3',5'-O-(di-tert-butyl)silyl-2'-O-dimethyl(tert-butyl)silylinosine 在 吡啶 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 氟化氢吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 30.84h， 生成 5'-O-(4,4'-dimethoxytrityl)-3'-O-[(2-cyanoethoxy)(N,N-diisopropylamino)phosphino]-2'-O-(t-butyldimethylsilyl)-N⁶-methyladenosine
  参考文献：
  名称：

  通过 BOP 介导的 SNAr 反应改进亚磷酰胺保护的 N6-甲基腺苷的合成

  摘要：

  N6-甲基腺苷 (m6A) 是 mRNA 中最丰富的修饰。对引入和结合 m6A 的蛋白质的研究需要有效合成含有 m6A 的寡核苷酸。我们报告了从肌苷开始的 m6A 亚磷酰胺的改进的五步合成，在关键步骤中利用 1-H-苯并三唑-1-基氧基三（二甲氨基）鏻六氟磷酸盐（BOP）介导的 SNAr 反应。与报道的路线相比，该路线的总产量显着增加，并且可用于合成其他腺苷衍生物的亚磷酰胺，例如乙醇腺苷，一种由重要的抗癌药物卡莫司汀形成的 DNA 加合物的 RNA 类似物。

  DOI：

  10.3390/molecules26010147
• 作为产物：
  描述：

  肌苷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 3',5'-O-(di-tert-butyl)silyl-2'-O-dimethyl(tert-butyl)silylinosine
  参考文献：
  名称：

  Polymorphism of the Signaling Molecule c-di-GMP

  摘要：

  Using UV, CD, and NMR, we demonstrate that the important bacterial signaling molecule involved in biofilm formation, cyclic diguanosine monophosphate (c-di-GMP), exists as a mixture of five different but related structures in an equilibrium that is sensitive both to its concentration and to the metal present. At the lower concentrations used for UV and CD work (0.05-0.5 mM), Li+, Na+, Cs+, and Mg2+ favor a bimolecular self-intercalated structure, while K+, Rb+, and NH4+ favor formation of one or more guanine quartet complexes as well. At the higher NMR concentrations (similar to 30 mM), the bimolecular structures associate and rearrange to a mixture of all-syn and all-anti tetramolecular and octamolecular quartet complexes. With K+ the octamolecular complexes predominate, while with Li+ the tetramolecular and octamolecular quartet complexes are present in approximately equal amounts, along with the bimolecular structure. We also find that both guanine amino groups in c-di-GMP are essential for formation of the quartets, because substitution of inosine for one guanosine allows formation of only the bimolecular structure. Further, two molecules of c-di-GMP tethered together are constrained in such a way that limits their ability to form these quartet complexes. The polymorphism we describe may provide different options for this signaling molecule when performing its functions in a bacterial cell, with K+ and its own local concentration controlling the equilibrium.

  DOI：

  10.1021/ja0613714

文献信息

• Structure-Based Design of Selective Fat Mass and Obesity Associated Protein (FTO) Inhibitors
  作者：Shifali Shishodia、Marina Demetriades、Dong Zhang、Nok Yin Tam、Pratheesh Maheswaran、Caitlin Clunie-O’Connor、Anthony Tumber、Ivanhoe K. H. Leung、Yi Min Ng、Thomas M. Leissing、Afaf H. El-Sagheer、Eidarus Salah、Tom Brown、Wei Shen Aik、Michael A. McDonough、Christopher J. Schofield

  DOI：10.1021/acs.jmedchem.1c01204

  日期：2021.11.25

  complex with 2OG and substrate mimics, we designed and synthesized two series of FTO inhibitors, which were characterized by turnover and binding assays, and by X-ray crystallography with FTO and the related bacterial enzyme AlkB. A potent inhibitor employing binding interactions spanning the FTO 2OG and substrate binding sites was identified. Selectivity over other clinically targeted 2OG oxygenases

  FTO 催化 Fe(II) 和 2-酮戊二酸 (2OG) 依赖性核酸修饰，包括 mRNA 中N 6 -甲基腺苷 (m 6 A) 的去甲基化。 FTO 是抗癌治疗的拟议靶标。利用 FTO 与 2OG 和底物模拟物复合物的晶体结构信息，我们设计并合成了两个系列的 FTO 抑制剂，通过周转和结合测定以及 FTO 和相关细菌酶 AlkB 的 X 射线晶体学对其进行了表征。鉴定出一种有效的抑制剂，其利用跨越 FTO 2OG 和底物结合位点的结合相互作用。与其他临床靶向 2OG 加氧酶相比，其选择性得到证实，包括缺氧诱导因子脯氨酰和天冬酰胺酰羟化酶（PHD2 和 FIH）以及选定的 JmjC 组蛋白去甲基酶 (KDM)。结果说明基于结构的设计如何能够识别有效且选择性的 2OG 加氧酶抑制剂，并将有助于开发体内使用的 FTO 抑制剂。
• Synthesis of a Cyclic Dinucleotide Analogue with Ambiguous Bases, 5-Aminoimidazole-4-carboxamide
  作者：Noriko S. Tarashima、Yusuke Kumanomido、Katsuyuki Nakashima、Yoshiyuki Tanaka、Noriaki Minakawa

  DOI：10.1021/acs.joc.1c01706

  日期：2021.11.5

  Cyclic dinucleotides (CDNs) are second messengers composed of two purine nucleotides. In recent years, the structural diversity of CDNs and their functionality in biological processes are being intensely studied. Herein we report the chemical synthesis of cyclic di-5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl monophosphate (c-di-ZMP) (1), which consists of two 5-amino-4-imidazolecarboxamide ribonucleotides

  环状二核苷酸 (CDN) 是由两个嘌呤核苷酸组成的第二信使。近年来，CDN的结构多样性及其在生物过程中的功能正在被深入研究。在此，我们报道了环状二-5-氨基咪唑-4-甲酰胺-1-β- d-呋喃核糖基单磷酸盐 (c-di-ZMP) ( 1 ) 的化学合成，它由两个 5-氨基-4-咪唑甲酰胺核糖核苷酸 ( Z-核糖核苷酸）通过两个磷酸二酯键连接。通过亚磷酰胺化学构建具有N 1 -二硝基苯基次黄嘌呤碱基 (Hxa DNP -base) 的 CDN 骨架，随后 Hxa DNP -base 的开环反应成功地产生了所需的1.
• Synthesis of RNA-cofactor conjugates and structural exploration of RNA recognition by an m6A RNA methyltransferase
  作者：Vincent Meynier、Laura Iannazzo、Marjorie Catala、Stephanie Oerum、Emmanuelle Braud、Colette Atdjian、Pierre Barraud、Matthieu Fonvielle、Carine Tisné、Mélanie Ethève-Quelquejeu

  DOI：10.1093/nar/gkac354

  日期：2022.6.10

  assays with RlmJ, a bacterial m6A rRNA methyltransferase. Two crystal structures of RlmJ in complex with RNA–SAM conjugates were solved and revealed the RNA-specific recognition elements used by RlmJ to clamp the RNA substrate in its active site. From these structures, a model of a trinucleotide bound in the RlmJ active site could be built and validated by methyltransferase assays on RlmJ mutants. The methyl

  RNA 缀合物的化学合成为研究 RNA 生物学中的酶学机制开辟了新的策略。为了深入了解了解甚少的 RNA 核苷酸甲基化过程，我们开发了一种合成 RNA 偶联物的新方法，用于研究 SAM 依赖性 m6A RNA 甲基转移酶的 RNA 识别和甲基转移机制。这些 RNA 偶联物含有一个 SAM 辅因子类似物，连接在二核苷酸、三核苷酸或 13 聚体 RNA 内腺苷的 N6 原子上。我们的化学途径具有化学和区域选择性，并允许灵活修改 RNA 长度和序列。这些化合物用于与细菌 m6A rRNA 甲基转移酶 RlmJ 的结晶测定。解决了与 RNA-SAM 缀合物复合的 RlmJ 的两种晶体结构，并揭示了 RlmJ 用于将 RNA 底物夹在其活性位点的 RNA 特异性识别元件。从这些结构中，可以通过对 RlmJ 突变体的甲基转移酶测定建立和验证在 RlmJ 活性位点中结合的三核苷酸模型。也可以推断出 RlmJ
• Synthesis of cyclic di-nucleotidic acids as potential inhibitors targeting diguanylate cyclase
  作者：Shi Min Ching、Wan Jun Tan、Kim Lee Chua、Yulin Lam

  DOI：10.1016/j.bmc.2010.07.068

  日期：2010.9

  Five analogs of cyclic di-nucleotidic acid including c-di-GMP were synthesized and evaluated for their biological activities on Slr1143, a diguanylate cyclase of Synechocystis sp. Slr1143 was overexpressed from the recombinant plasmid which contained the gene of interest and subsequently purified by affinity chromatography. A new HPLC method capable of separating the compound and product peaks with good resolution was optimized and applied to the analysis of the compounds. Results obtained show that cyclic di-inosinylic acid 1b demonstrates a stronger inhibition on Slr1143 than c-di-GMP and is a potential inhibitor for biofilm formation. (c) 2010 Elsevier Ltd. All rights reserved.