7-Methylguanin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 7-Methylguanin
• 英文别名: 2-Amino-7-methyl-1,9-dihydropurin-7-ium-6-one；2-amino-7-methyl-1,9-dihydropurin-7-ium-6-one
• 化学式: C₆H₈N₅O
• 分子量: 166.162
• InChiKey: FZWGECJQACGGTI-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  87.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  7-甲基鸟苷 在 Cu⁽²⁺⁾TerPy 、 水 作用下， 生成 卡培他滨杂质25 、 7-Methylguanin
  参考文献：
  名称：

  Metal ion-promoted cleavage of mRNA 5′-cap models: hydrolysis of the triphosphate bridge and reactions of the N7-methylguanine base

  摘要：

  对mRNA 5'端帽模型化合物的反应进行了研究，以评估这些反应在人工RNase开发中的潜力。二腺苷三磷酸被用作三磷酸桥的模型，并在几种Cu²⁺络合物存在下研究了其水解。动力学实验的结果表明，磷酸盐结合的Cu²⁺络合物参与了双功能催化。具有酸性水合配体的络合物实现了最有效的催化，而金属离子结合的羟基配体很可能在反应中起到亲核试剂的作用。然而，基于数据无法提出详细的机制。使用N7-甲基鸟苷及其5'单磷酸和二磷酸研究了mRNA 5'端帽部分的N7-甲基鸟嘌呤碱基的反应。尽管Cu²⁺络合物有效地增强了三磷酸桥的水解，但对N7-甲基鸟嘌呤碱基反应几乎没有影响：咪唑环的断裂或核苷的脱嘌呤反应并没有显著增强。

  DOI：

  10.1039/b108222a

文献信息

• [EN] 5'-PHOSPHOROTHIOLATE MRNA 5'-END (CAP) ANALOGS, MRNA COMPRISING THE SAME, METHOD OF OBTAINING AND USES THEREOF<br/>[FR] ANALOGUES D'EXTRÉMITÉ 5' (COIFFE) D'ARNM 5'-PHOSPHOROTHIOLATE , ARNM LES COMPRENANT, LEUR PROCÉDÉ D'OBTENTION ET UTILISATIONS
  申请人：UNIV WARSZAWSKI

  公开号：WO2017130151A1

  公开（公告）日：2017-08-03

  The present invention relates to nucleotides, analogs of mRNA 5'-end (cap) containing sulfur atom at the position 5' of 7-methylguanosine nucleoside. The disclosed compounds are recognized (bound and non-hydrolyzed) by DcpS enzyme (Decapping Scavenger), and thus may find therapeutic use as inhibitors thereof. DcpS is cap-specific enzyme with pyrophosphatase activity, which was identified as a therapeutic target in the treatment of spinal muscular atrophy (SMA). Some of the compounds disclosed have additional modifications in the phosphate chain, wh ich modulate their affinity for DcpS enzyme. The present invention also relates to mRNAs modified at the 5' end with mRNA 5'-end (cap) analogs containing 5'- phosphorothiolate moiety, which mRNAs have an increased stability and translational activity in cellular conditions, to a method of their preparation, their uses, and to a pharmaceutical formulation containing them, wherein L1 and L2 are independently selected from the group comprising O and S, wherein at least one of L1 and L2 is not O.

  本发明涉及核苷酸，含有硫原子的mRNA 5'-端（帽子）的类似物，在7-甲基鸟苷核苷酸的5'位置。所公开的化合物被DcpS酶（去帽清道夫）识别（结合并不水解），因此可能作为其抑制剂在治疗中发挥作用。DcpS是帽子特异性酶，具有焦磷酸酶活性，已被确定为治疗脊髓性肌萎缩（SMA）的治疗靶点。所公开的一些化合物在磷酸链中具有额外的修饰，调节它们对DcpS酶的亲和力。本发明还涉及在mRNA的5'端修饰了含有5'-磷硫酸酯基团的mRNA 5'-端（帽子）类似物的mRNAs，这些mRNAs在细胞条件下具有增强的稳定性和翻译活性，以及它们的制备方法，用途和含有它们的制药配方，其中L1和L2分别选择自包括O和S的组中，其中至少一个L1和L2不是O。
• [EN] MRNA CAP ANALOGS AND METHODS OF MRNA CAPPING<br/>[FR] ANALOGUES DE COIFFES ARNM ET PROCÉDÉS DE COIFFAGE D'ARNM
  申请人：MODERNATX INC

  公开号：WO2017066793A1

  公开（公告）日：2017-04-20

  The present disclosure relates to cap analogs of formula (I) as defined in claim 1, which can result in high levels of capping efficiency and transcription and improved translation efficiencies. The present disclosure also relates to methods useful for preparing cap analogs and using mRNA species containing such analogs, as well as kits containing the novel cap analogs.

  本公开涉及公式（I）中定义的帽子类似物，其可以导致高水平的帽子效率和转录以及改善的翻译效率。本公开还涉及用于制备帽子类似物和使用包含此类类似物的mRNA物种的方法，以及包含新型帽子类似物的试剂盒。
• [EN] TRINUCLEOTIDE MRNA CAP ANALOGS<br/>[FR] ANALOGUES DE COIFFES D'ARNM TRINUCLÉOTIDIQUES
  申请人：MODERNATX INC

  公开号：WO2017066797A1

  公开（公告）日：2017-04-20

  The present disclosure relates to cap analogs of formula (I) as defined in claim 1, which can result in high levels of capping efficiency and transcription and improved translation efficiencies. The present disclosure also relates to methods useful for preparing cap analogs and using mRNA species containing such analogs, as well as kits containing the novel cap analogs.