8-methyl-2'-deoxyguanosine | 85819-69-8

• 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: 8-methyl-2'-deoxyguanosine
• 英文别名: 2-Amino-9-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-8-methyl-1H-purin-6(9H)-one；2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-methyl-1H-purin-6-one
• CAS: 85819-69-8
• 化学式: C₁₁H₁₅N₅O₄
• 分子量: 281.271
• InChiKey: GXBIHETUJVTBJG-RRKCRQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  6

制备方法与用途

8-甲基-2'-脱氧鸟苷是一种嘌呤核苷类似物，具有广泛抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要通过抑制DNA合成和诱导细胞凋亡来实现。

反应信息

• 作为反应物：
  描述：

  8-methyl-2'-deoxyguanosine 在 吡啶 、 4-二甲氨基吡啶 、 三甲基氯硅烷 、 三乙胺 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 3'-O-[(2-cyanoethoxy)(diisopropylamino)phosphino]-5'-O-(4,4'-dimethoxytrityl)-N²-isobutyryl-8-methyl-2'-deoxyguanosine
  参考文献：
  名称：

  Synthesis, Miscoding Specificity, and Thermodynamic Stability of Oligodeoxynucleotide Containing 8-Methyl-2‘-deoxyguanosine

  摘要：

  8-Methyl-2'-deoxyguanosine (8-MedG) was synthesized by reacting dG under the methyl radical generating system and incorporated into oligodeoxynucleotides using phosphoramidite techniques. The site-specifically modified oligodeoxynucleotide containing a single 8-MedG was then used as a template for primer extension reactions catalyzed by the 3'-5' exonuclease-free (exo(-)) Klenow fragment of Escherichia coli DNA polymerase I and mammalian DNA polymerase alpha. Primer extension catalyzed by the exo(-) Klenow fragment, readily passed the 8-MedG lesion in the template while that catalyzed by pol alpha was retarded opposite the lesion. The fully extended products formed during DNA synthesis were analyzed to quantify the miscoding specificities of 8-MedG;. Both DNA polymerases incorporated primarily dCMP, the correct base opposite the lesion, along with small amounts of incorporation of dAMP and dAMP. In addition, two-base deletion was observed only when the exo(-) Klenow fragment was used. The thermodynamic stability of 8-MedG in the duplex was also studied. The duplex containing 8-MedG:dG was more thermally and thermodynamically stable than that of dG:dG. The duplex containing 8-MedG:dA was more thermodynamically stable than that of dG:dA. We conclude that 8-MedG is a miscoding lesion and capable of generating G --> C and G --> T transversions and deletion in cells.

  DOI：

  10.1021/tx9601059
• 作为产物：
  描述：

  3',5'-di-O-acetyl-8-methyl-2'-deoxyguanosine 在 氨 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以78%的产率得到8-methyl-2'-deoxyguanosine
  参考文献：
  名称：

  Structure-Activity Study of Oligodeoxynucleotides Which Inhibit Thrombin

  摘要：

  The 15-mer oligodeoxynucleotide GGTTGGTGTGGTTGG is a potent inhibitor of thrombin and it forms a stable, highly compact structure in solution. Deletions and substitutions by abasic residues, 2'-deoxyinosine, 7-deaza-2'-deoxyguanosine and 8-methyl-2'-deoxyguanosine show that the structural features of the oligodeoxynucleotide are important for its biological activity.

  DOI：

  10.1080/15257779508012546

文献信息

• 2‘-Deoxyguanosine (DG) Oxidation and Strand-Break Formation in DNA by the Radicals Released in the Photolysis of <i>N</i>-<i>tert</i>-Butoxy-2-pyridone. Are <i>tert</i>-Butoxyl or Methyl Radicals Responsible for the Photooxidative Damage in Aqueous Media?
  作者：Waldemar Adam、Stefan Marquardt、Diana Kemmer、Chantu R. Saha-Möller、Peter Schreier

  DOI：10.1021/ol016955j

  日期：2002.1.1

  releases tert-butoxyl radicals, which have been trapped by DMPO and EPR-spectrally identified. In aqueous solution, however, the fragmentation of the tert-butoxyl into methyl radicals prevails and the former radicals are of no direct consequence in the photooxidation of 2'-deoxyguanosine (dG) and pBR 322 DNA. The photooxidative damage of nucleic acids is caused by the oxyl radical species generated from

  [反应：见正文]吡啶酮3b（光芬顿试剂）在苯中的光解释放出叔丁氧基，这些自由基已被DMPO和EPR光谱鉴定。然而，在水溶液中，叔丁氧基断裂成甲基基团占主导，而前者基团对2'-脱氧鸟苷（dG）和pBR 322 DNA的光氧化没有直接影响。核酸的光氧化损伤是由甲基自由基与氧气产生的羟基自由基引起的。
• Addition of Deoxyribose to Guanine and Modified DNA Bases by <i>Lactobacillus helveticus</i> <i>trans</i>-<i>N</i>-Deoxyribosylase
  作者：Michael Müller、Linda K. Hutchinson、F. Peter Guengerich

  DOI：10.1021/tx9600661

  日期：1996.1.1

  trans-N-deoxyribosylase was evaluated as an alternative method for deoxyribosylation in the synthesis of deoxyribonucleosides containing potentially mutagenic adducts. A crude enzyme preparation was isolated from Lactobacillus helveticus and compared to Escherichia coli purine nucleoside phosphorylase. trans-N-deoxyribosylase was more regioselective than purine nucleoside phosphorylase in the deoxyribosylation of

  细菌反式-N-脱氧核糖基化酶的使用已被评估为合成含潜在诱变加合物的脱氧核糖核苷的一种替代方法。从瑞士乳杆菌中分离出粗制酶制剂，并将其与大肠杆菌嘌呤核苷磷酸化酶进行比较。如产物的NMR分析所示，与N7相比，在N9原子处的Gua的脱氧核糖基化中，反式N-脱氧核糖基化酶比嘌呤核苷磷酸化酶具有更高的区域选择性。5,6,7,9-四氢-7-乙酰氧基-9-氧代咪唑并[1,2-a]嘌呤可被反式-N-脱氧核糖基化酶有效地脱氧核糖基化，而根本不被嘌呤核苷磷酸化酶完全脱氧。反式-N-脱氧核糖基化酶的其他底物是N2-（2-氧乙基）Gua，嘧啶并[1,2-a]嘌呤-10（3H）-one，1，N2-ε-Gua，N2,3-ε-Gua ，3，N4-ε-Cyt，1，N6-ε-Ade，C8-甲基瓜瓜和C8-氨基瓜瓜，其中大多数以良好的收率得到了所需的异构体（与瓜9中的N9对应的氮键）。N7-烷基嘌呤和C8-（芳基氨基）取代的
• Novel guanosine derivatives and use thereof
  申请人：Sugiyama Hiroshi

  公开号：US20060235219A1

  公开（公告）日：2006-10-19

  It is intended to provide a novel monomer unit by which Z type DNA can be more effectively stabilized, a reagent for integrating this monomer unit into an oligonucleotide, and a method of stabilizing Z type DNA by using the reagent. Namely, a guanosine derivative represented by the following general formula [1]: wherein R 1 represents acyl; R 2 represents lower alkyl; R 3 represents tri-substituted silyloxy or tetrahedropyranyloxy; and R 4 represents cyanoethyl or allyl; a reagent for stabilizing Z type DNA which contains the guanosine derivative; and a method of stabilizing Z type DNA by using the guanosine derivative. It is also intended to provide a method of transferring guanosine having lower alkyl at the 8-position into an oligonucleotide by using the guanosine derivative; and an oligonucleotide carrying guanosine having lower alkyl at the 8-position transferred thereinto.

  本发明旨在提供一种新型单体单元，通过该单元可以更有效地稳定Z型DNA，一种将该单体单元集成到寡核苷酸中的试剂，以及使用该试剂稳定Z型DNA的方法。即以下通式[1]所表示的鸟苷衍生物：其中，R1代表酰基；R2代表低级烷基；R3代表三取代硅氧烷基或四氢吡喃氧基；R4代表氰乙基或烯丙基；还包括一种含有该鸟苷衍生物的稳定Z型DNA的试剂，以及使用该鸟苷衍生物稳定Z型DNA的方法。本发明还旨在提供一种使用该鸟苷衍生物将8-位低级烷基鸟苷转移至寡核苷酸中的方法，以及携带转移后8-位低级烷基鸟苷的寡核苷酸。
• NOVEL GUANOSINE DERIVATIVES AND USE THEREOF
  申请人：Japan Science and Technology Agency

  公开号：EP1604995A1

  公开（公告）日：2005-12-14

  It is intended to provide a novel monomer unit by which Z type DNA can be more effectively stabilized, a reagent for integrating this monomer unit into an oligonucleotide, and a method of stabilizing Z type DNA by using the reagent. Namely, a guanosine derivative represented by the following general formula [1]: wherein R1 represents acyl; R2 represents lower alkyl; R3 represents tri-substituted silyloxy or tetrahedropyranyloxy; and R4 represents cyanoethyl or allyl; a reagent for stabilizing Z type DNA which contains the guanosine derivative; and a method of stabilizing Z type DNA by using the guanosine derivative. It is also intended to provide a method of transferring guanosine having lower alkyl at the 8-position into an oligonucleotide by using the guanosine derivative; and an oligonucleotide carrying guanosine having lower alkyl at the 8-position transferred thereinto.

  本发明旨在提供一种可以更有效地稳定 Z 型 DNA 的新型单体单元、一种将该单体单元整合到寡核苷酸中的试剂以及一种使用该试剂稳定 Z 型 DNA 的方法。即由以下通式[1]代表的鸟苷衍生物： 其中 R1 代表酰基；R2 代表低级烷基；R3 代表三取代的硅氧基或四取代的吡喃氧基；以及 R4 代表氰乙基或烯丙基；一种稳定 Z 型 DNA 的试剂，其中含有该鸟苷衍生物；以及一种通过使用该鸟苷衍生物稳定 Z 型 DNA 的方法。本发明还旨在提供一种通过使用鸟苷衍生物将在 8 位上具有低级烷基的鸟苷转移到寡核苷酸中的方法；以及一种携带在 8 位上具有低级烷基的鸟苷的寡核苷酸。
• Stability of <i>N</i>-Glycosidic Bond of (5′<i>S</i>)-8,5′-Cyclo-2′-deoxyguanosine
  作者：Rajat S. Das、Milinda Samaraweera、Martha Morton、José A. Gascón、Ashis K. Basu

  DOI：10.1021/tx300302a

  日期：2012.11.19

  8,5'-Cyclopurine deoxynucleosides are unique tandem lesions containing an additional covalent bond between the base and the sugar. These mutagenic and genotoxic lesions are repaired only by nucleotide excision repair. The N-glycosidic (or C1'-N9) bond of 2'-deoxyguanosine (dG) derivatives is usually susceptible to acid hydrolysis, but even after cleavage of this bond of the cyclopurine lesions, the base would remain attached to the sugar. Here, the stability of the N-glycosidic bond and the products formed by formic acid hydrolysis of (5'S)-8,5'-cyclo-2'-deoxyguanosine (S-cdG) were investigated. For comparison, the stability of the N-glycosidic bond of 8,5'-cyclo-2',5'-dideoxyguanosine (ddcdG), 8-methyl-2'-deoxyguanosine (8-Me-dG), 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-Oxo-dG), and dG was also studied. In various acid conditions, S-cdG and ddcdG exhibited similar stability to hydrolysis. Likewise, 8-Me-dG and dG showed comparable stability, but the half-lives of the cyclic dG lesions were at least 5-fold higher than those of dG or 8-Me-dG. NMR studies were carried out to investigate the products formed after the cleavage of the C1'-N9 bond. 2-Deoxyribose generated alpha and beta anomers of deoxyribopyranose and deoxyribopyranose oligomers following acid treatment. S-cdG gave alpha- and beta-deoxyribopyranose linked guanine as the major products, but alpha and beta anomers of deoxyribofuranose linked guanine and other products were also detected. The N-glycosidic bond of 8-Oxo-dG was found exceptionally stable in acid. Computational studies determined that both the protonation of the N7 atom and the rate constant in the bond breaking step control the overall kinetics of hydrolysis, but both varied for the molecules studied indicating a delicate balance between the two steps. Nevertheless, the computational approach successfully predicted the trend observed experimentally. For 8-Oxo-dG, the low pK(a) of O-8 and N3 prevented appreciable protonation, making the free energy for N-glycosidic bond cleavage in the subsequent step very high.