3',5'-bis-O-(tert-butyldimethylsilyl)-2'-O-methyladenosine | 251296-61-4

• 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'-bis-O-(tert-butyldimethylsilyl)-2'-O-methyladenosine
• 英文别名: 3',5'-O-bis(tert-butyldimethylsilyl)-2'-O-methyladenosine；TBDMS(-3)[TBDMS(-5)]Ribf2Me(b)-adenin-9-yl；9-[(2R,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-methoxyoxolan-2-yl]purin-6-amine
• CAS: 251296-61-4
• 化学式: C₂₃H₄₃N₅O₄Si₂
• 分子量: 509.797
• InChiKey: PEIOYADVKSQEEX-QTQZEZTPSA-N

物化性质

• 熔点：
  100-103 °C
• 沸点：
  553.2±60.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.73
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3',5'-bis-O-(tert-butyldimethylsilyl)-2'-O-methyladenosine 在 吡啶 、 4-二甲氨基吡啶 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 84.75h， 生成 5'-O-(4,4'-dimethoxytrityl)-6-N-[N-(trans-4-levulinyloxycyclohexyl)carbamoyl]-2'-O-methyladenosine 3'-(2-cyanoethyl N,N-diisopropylphosphoramidite)
  参考文献：
  名称：

  使用具有环己基磷酸酯作为取代基的腺苷和鸟苷衍生物修饰的寡核苷酸的短RNA选择性结合†

  摘要：

  我们开发了新的人工寡核苷酸，可将短RNA靶与长RNA靶区分开。通过使用具有庞大体积的腺苷衍生物修饰寡核苷酸的5'末端磷酸环己基酯 在其碱基部分上的部分和在其位置上的磷酸基团 5'-羟基小组最大程度地提高了其短RNA选择性。这2′- O-甲基-RNA （5′-XC m A m A m C m C m U m A m C m U m具有这些修饰的）约 高10°CŤ米 互补的短RNA（3'-GUUGGAUGA-5'）的双链体比长RNA（3′-AUUAUAU UGGUUA-5''）。具有相同修饰的寡脱氧核苷酸表现出相似的选择性。末端修饰的寡核苷酸的这种短RNA选择性结合可用于区分成熟的microRNA和前microRNA。

  DOI：

  10.1039/c1ob06580g
• 作为产物：
  描述：

  腺苷 在 咪唑 、 4-二甲氨基吡啶 、 四丁基碘化铵 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 3',5'-bis-O-(tert-butyldimethylsilyl)-2'-O-methyladenosine
  参考文献：
  名称：

  Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

  摘要：

  The adenylation (A) domain is essential for non-ribosomal peptide synthetases (NRPSs), which synthesize various peptide-based natural products, including virulence factors, such as siderophores and genotoxins. Hence, the inhibition of A-domains could attenuate the virulence of pathogens. 5’-O-N-(Aminoacyl or arylacyl)sulfamoyladenosine (AA-AMS) is a bisubstrate small-molecule inhibitor of the A-domains of NRPSs. However, the bacterial cell permeability of AA-AMS is typically a problem owing to its high hydrophilicity. In this study, we investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors.

  DOI：

  10.3762/bjoc.20.39

文献信息

• [EN] S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS<br/>[FR] POLYMÈRES OLIGONUCLÉOTIDIQUES INHIBANT LE TRANSPORT DE L'ANTIGÈNE S ET MÉTHODES
  申请人：ALIGOS THERAPEUTICS INC

  公开号：WO2021119325A1

  公开（公告）日：2021-06-17

  Various embodiments provide STOPS™ polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS™ modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS™ modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.

  各种实施方式提供了STOPS™聚合物，这些聚合物是S-抗原转运抑制寡核苷酸聚合物，提供了制备它们的方法以及使用它们治疗疾病和症状的方法。在某些实施方式中，STOPS™修饰的寡核苷酸包括至少部分磷硫酸酯化的交替A和C单元序列，具有如本文所述的修饰。通过HBsAg分泌测定确定的STOPS™修饰的寡核苷酸对乙型肝炎的序列无关抗病毒活性，其EC50小于100 nM。
• Modified Short Interfering Nucleic Acid (siNA) Molecules and Uses Thereof
  申请人：Aligos Therapeutics, Inc.

  公开号：US20220177888A1

  公开（公告）日：2022-06-09

  Disclosed herein are short interfering nucleic acid (siNA) molecules comprising modified nucleotides and uses thereof. The siNA molecules may be double stranded and comprise modified nucleotides selected from 2′-O-methyl nucleotides and 2′-fluoro nucleotides. Further disclosed herein are siNA molecules comprising (a) a phosphorylation blocker, conjugated moiety, or 5′-stabilized end cap; and (b) a short interfering nucleic acid (siNA).

  本文披露了包含修饰核苷酸的短干扰核酸（siNA）分子及其用途。siNA分子可以是双链的，并包括从2'-O-甲基核苷酸和2'-氟核苷酸中选择的修饰核苷酸。本文还披露了包含（a）磷酸化阻断剂、共轭基团或5'-稳定端盖；以及（b）短干扰核酸（siNA）的siNA分子。
• WO2020097342A5
  申请人：——

  公开号：WO2020097342A5

  公开（公告）日：2022-11-11
• Amide-Linked Ribonucleoside Dimers Derived from 5‘-Amino-5‘-deoxy- and 3‘-(Carboxymethyl)-3‘-deoxynucleoside Precursors¹
  作者：Matt A. Peterson、Bradley L. Nilsson、Sanchita Sarker、Bogdan Doboszewski、Weijian Zhang、Morris J. Robins

  DOI：10.1021/jo9908647

  日期：1999.10.1

  Treatment of tert-butyldimethylsilyl (TBDMS) derivatives of 3'-keto(adenosine or uridine) with [(ethoxycarbonyl)methylene]triphenylphosphorane gave exocyclic alkenes that underwent stereoselective hydrogenation to give 3'-deoxy-3'-[(ethoxycarbonyl)methyl](Ado or Urd) analogues. Saponification provided the 3'-(carboxymethyl)-3'-deoxy(Ado and Urd) derivatives 37 and 38. Treatment of 37 or 38 with DCC and 5'-amino-2',3'-bis-O-TBDMS-5'-deoxynucleosides gave the amide-linked dimers (74-82%). Activation of 37 or 38 with 4-nitrophenol/DCC, and direct coupling of the 4-nitrophenyl esters with 5'-amino-5'-deoxy(Ado or Urd) in pyridine also produced amide dimers efficiently (65-70%). Analogous activation of a 5'-O-DMT-protected carboxylate, and its coupling with 5'-amino-5'-deoxy-2'-O-methyladenosine gave the amide dimer in good yield (74%). Coupling (DCC) of a 5'-azido-2'-O-TBDMS-3'-(carboxymethyl)-3', 5'-dideoxyuridine intermediate with 5'-amino-5'-deoxynucleosides gave amide-linked dimers (72-78%) that can serve as masked (azide reduction) 5'-amino dimers for analogous synthesis of extended amide-linked oligomers.
• Recognition and detection of 8-oxo-rG in RNA using the DNA/OMeRNA chimera probes containing fluorescent adenosine-diazaphenoxazine analog
  作者：Yohei Koga、Yosuke Taniguchi、Yoshiya Kikukawa、Shigeki Sasaki

  DOI：10.1016/j.bmc.2016.02.001

  日期：2016.3

  Recent studies indicate that oxidative damage to RNA results in dysfunction of translation and eventual pathogenesis. A representative oxidized base in RNA is 8-hydroxyguanosine (8-oxo-rG), however, unlike its DNA counterpart (8-oxo-dG), its role in pathogenesis has not attracted much attention until recently. The 2'-deoxyadenosine derivative with a diazaphenoxazine skeleton at the 6 -amino group (Adap) was shown to be selective for 8-oxo-dG in DNA. In this study, the 2'-0-methoxy derivative of Adap (2'-0MeAdap) was designed as a selective molecule for 8-oxo-rG in RNA. 8-Oxo-rG in the homopurine RNA was selectively recognized by the ODN probe incorporating Adap. In contrast, although it was not possible by the Adap-containing ODN prove due to the instability of the corresponding duplex, 8-oxorG in homopyrimidine RNA was selectively detected by the 2'-0MeRNA probe incorporating 2'-0MeAdap. (C) 2016 Published by Elsevier Ltd.