m⁷GpppG | 959909-41-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: m⁷GpppG
• 英文别名: (N(7)-methyl 5'-triphospho-guanosine)-guanosine；[[(2R,3S,4R,5R)-5-(2-amino-7-methyl-6-oxo-1H-purin-9-ium-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] phosphate
• CAS: 959909-41-2
• 化学式: C₂₁H₂₇N₁₀O₁₈P₃
• 分子量: 800.423
• InChiKey: FHHZHGZBHYYWTG-INFSMZHSSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -5.9
• 重原子数：
  52
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  439
• 氢给体数：
  8
• 氢受体数：
  25

反应信息

• 作为反应物：
  描述：

  m⁷GpppG 在 10-(imidazol-4-yl-CH₂)tetraazacyclotetradecaphane derivative 作用下， 生成 、 7-methylguanosine 5'-diphosphate 、 7-methylguanosine 5'-monophosphate 、 GDP
  参考文献：
  名称：

  Regio-selective synthesis of polyazacyclophanes incorporating a pendant group as potential cleaving agents of mRNA 5′-cap structure

  摘要：

  A terpyridine or an imidazole unit has been tethered to an N-protected polyazacyclophane to give the appropriate N-monofunctionalized polyazacyclophane. After mild deprotection, four polyazacyclophanes incorporating a pendant group were obtained in satisfactory yields. Their preliminary cleavage ability of mRNA 5'-cap model was studied at pH 7.2. Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2007.08.102
• 作为产物：
  描述：

  鸟苷酸 在 N-ethylmorpholine buffer 、 triphenylphosphine-dipyridyl disulfide 、 三乙基碳酸氢铵缓冲液 、 manganese(ll) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 生成 m⁷GpppG
  参考文献：
  名称：

  Facile synthesis of cap portion of messenger RNA by Mn(II) ion-catalyzed pyrophosphate formation in aqueous solution

  摘要：

  Cap portion of messenger RNA was prepared by Mn2+ ion-catalyzed pyrophosphate bond formation from 7-methylguanosine-5'-phosphorimidazolide and nucleoside diphosphate in neutral aqueous solution.

  DOI：

  10.1016/0040-4039(91)80440-h

文献信息

• Identification of a quality-control mechanism for mRNA 5′-end capping
  作者：Xinfu Jiao、Song Xiang、ChanSeok Oh、Charles E. Martin、Liang Tong、Megerditch Kiledjian

  DOI：10.1038/nature09338

  日期：2010.9.30

  Following their transcription, eukaryotic messenger RNAs have a 7-methylguanosine cap added to their 5′ ends to protect the mRNA from degradation. Xinfu Jiao et al. show that caps lacking a methyl group are recognized by Rai1, which clips off the incomplete cap. These data suggest that Rai1 is part of a quality-control mechanism that monitors and promotes the digestion of aberrant mRNAs that may arise during stress conditions. Following their synthesis, eukaryotic messenger RNAs have a 7-methylguanosine cap added to their 5′ ends to protect the mRNAs from degradation. Here it is shown that, in vitro and in yeast, caps lacking a methyl group are recognized by the Rai1 protein, which clips off the incomplete cap. The data provide evidence that Rai1 is part of a quality-control mechanism that monitors, and promotes the digestion of, aberrant mRNAs that might arise during stress conditions. The 7-methylguanosine cap structure at the 5′ end of eukaryotic messenger RNAs is a critical determinant of their stability and translational efficiency1,2,3. It is generally believed that 5′-end capping is a constitutive process that occurs during mRNA maturation and lacks the need for a quality-control mechanism to ensure its fidelity. We recently reported that the yeast Rai1 protein has pyrophosphohydrolase activity towards mRNAs lacking a 5′-end cap4. Here we show that, in vitro as well as in yeast cells, Rai1 possesses a novel decapping endonuclease activity that can also remove the entire cap structure dinucleotide from an mRNA. This activity is targeted preferentially towards mRNAs with unmethylated caps in contrast to the canonical decapping enzyme, Dcp2, which targets mRNAs with a methylated cap. Capped but unmethylated mRNAs generated in yeast cells with a defect in the methyltransferase gene are more stable in a rai1-gene-disrupted background. Moreover, rai1Δ yeast cells with wild-type capping enzymes show significant accumulation of mRNAs with 5′-end capping defects under nutritional stress conditions of glucose starvation or amino acid starvation. These findings provide evidence that 5′-end capping is not a constitutive process that necessarily always proceeds to completion and demonstrates that Rai1 has an essential role in clearing mRNAs with aberrant 5′-end caps. We propose that Rai1 is involved in an as yet uncharacterized quality control process that ensures mRNA 5′-end integrity by an aberrant-cap-mediated mRNA decay mechanism.

  。
• An effective method for the synthesis of the cap structure of eukaryotic messenger ribonucleic acids
  作者：Takashi Kamimura、Yumi Osaki、Mitsuo Sekine、Tsujiaki Hata

  DOI：10.1016/s0040-4039(01)81262-4

  日期：1984.1
• Synthesis and Properties of P1, P2-, P1, P3- and P1, P4-Dinucleoside Di-, Tri- and Tetraphosphate mRNA 5'-Cap Analogues
  作者：J. Steogon、pinski、M. Bretner、M. Jankowska、K. Felczak、R. Stolarski、Z. Wieczorek、A-L. Caipostalcode、R. E. Rhoads、A. Temeriusz、D. Haber、E. Darzynkiewicz

  DOI：10.1080/15257779508012457

  日期：1995.5.1
• A Mammalian Pre-mRNA 5′ End Capping Quality Control Mechanism and an Unexpected Link of Capping to Pre-mRNA Processing
  作者：Xinfu Jiao、Jeong Ho Chang、Turgay Kilic、Liang Tong、Megerditch Kiledjian

  DOI：10.1016/j.molcel.2013.02.017

  日期：2013.4

  Recently, we reported that two homologous yeast proteins, Rail and Dxo1, function in a quality control mechanism to clear cells of incompletely 5' end-capped messenger RNAs (mRNAs). Here, we report that their mammalian homolog, Dom3Z (referred to as DXO), possesses pyrophosphohydrolase, decapping, and 5'-to-3' exoribonuclease activities. Surprisingly, we found that DXO preferentially degrades defectively capped pre-mRNAs in cells. Additional studies show that incompletely capped pre-mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly cleaved for polyadenylation. Crystal structures of DXO in complex with substrate mimic and products at a resolution of up to 1.5 angstrom provide elegant insights into the catalytic mechanism and molecular basis for their three apparently distinct activities. Our data reveal a pre-mRNA 5' end capping quality control mechanism in mammalian cells, indicating DXO as the central player for this mechanism, and demonstrate an unexpected intimate link between proper 5' end capping and subsequent pre-mRNA processing.
• Regio-selective synthesis of polyazacyclophanes incorporating a pendant group as potential cleaving agents of mRNA 5′-cap structure
  作者：Zhibo Zhang、Satu Mikkola、Harri Lonnberg

  DOI：10.1016/j.tet.2007.08.102

  日期：2007.11

  A terpyridine or an imidazole unit has been tethered to an N-protected polyazacyclophane to give the appropriate N-monofunctionalized polyazacyclophane. After mild deprotection, four polyazacyclophanes incorporating a pendant group were obtained in satisfactory yields. Their preliminary cleavage ability of mRNA 5'-cap model was studied at pH 7.2. Published by Elsevier Ltd.