N¹-Methyl-guanosin-5'-guanosin | 20309-92-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: N¹-Methyl-guanosin-5'-guanosin
• 英文别名: 1-N-Methylguanosine-5'-phosphate；1-methyl-[5']guanylic acid；1-Methylguanosine 5'-(dihydrogen phosphate)；[(2R,3S,4R,5R)-5-(2-amino-1-methyl-6-oxopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 20309-92-6
• 化学式: C₁₁H₁₆N₅O₈P
• 分子量: 377.25
• InChiKey: RQNAZTAAOUHEIL-KQYNXXCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  193
• 氢给体数：
  5
• 氢受体数：
  10

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。
• MODIFIED NUCLEIC ACID MOLECULES AND USES THEREOF
  申请人：MODERNA THERAPEUTICS, INC.

  公开号：US20150307542A1

  公开（公告）日：2015-10-29

  The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them.

  本公开提供了修改的核苷酸，核苷酸和核酸，以及使用它们的方法。
• HIGH EXPRESSION mRNA SWITCH
  申请人：Kyoto University

  公开号：EP3653710A1

  公开（公告）日：2020-05-20

  The present invention provides an mRNA switch which has improved expression level and sensitivity. An mRNA comprising: (i) a nucleic acid sequence specifically recognized by a miRNA or protein; and (ii) a nucleic acid sequence corresponding to a coding region for a marker protein, wherein a nucleotide contained in the mRNA comprises N1-methyl pseudouridine.

  本发明提供了一种 mRNA 开关，它具有更好的表达水平和灵敏度。一种 mRNA 包括：(i) 被 miRNA 或蛋白质特异性识别的核酸序列；(ii) 与标记蛋白质编码区相对应的核酸序列，其中 mRNA 所含的核苷酸包括 N1-甲基假尿苷。
• 5'-PHOSPHOROTHIOLATE MRNA 5'-END (CAP) ANALOGS, MRNA COMPRISING THE SAME, METHOD OF OBTAINING AND USES THEREOF
  申请人：Uniwersytet Warszawski

  公开号：EP3408276A1

  公开（公告）日：2018-12-05
• De novo DNA cytosine methyltransferase genes, polypeptides and uses thereof
  申请人：The General Hospital Corporation

  公开号：US20040234997A1

  公开（公告）日：2004-11-25

  De novo DNA cytosine methyltransferase polynucleotides and polypeptides and methods for producing said polypeptides are disclosed. Also disclosed are methods for utilizing de novo DNA cytosine methyltransferase polynucleotides and polypeptides in diagnostic assays, in vitro DNA methylation assays for screening agonists and antagonists, and therapeutic applications such as the treatment of neoplastic disorders.