9-(2,3-dideoxy-β-D-ribofuranosyl)-6-methylpurine

• 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: 9-(2,3-dideoxy-β-D-ribofuranosyl)-6-methylpurine
• 英文别名: [(2S,5R)-5-(6-methylpurin-9-yl)oxolan-2-yl]methanol
• 化学式: C₁₁H₁₄N₄O₂
• 分子量: 234.258
• InChiKey: YEOFFKCPMNBENS-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  17
• 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：
  73.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2',3'-二脱氧肌苷 在 purine nucleoside 2’-deoxyribosyltransferase from Trypanosoma brucei 作用下， 以 aq. phosphate buffer 为溶剂， 反应 8.0h， 生成 9-(2,3-dideoxy-β-D-ribofuranosyl)-6-methylpurine
  参考文献：
  名称：

  使用来自布鲁氏锥虫的高度通用的嘌呤核苷2'-脱氧核糖基转移酶酶促合成治疗性核苷

  摘要：

  与多步化学方法相比，使用酶来合成核苷类似物具有多个优势，包括化学，区域和立体选择性以及较温和的反应条件。本文报道了来自布鲁氏锥虫的嘌呤核苷2'-脱氧核糖基转移酶（PDT）的生产，表征和利用。Tb PDT是一种二聚体，不仅在很宽的温度范围（50–70°C），pH（4–7）和离子强度（0–500 mM NaCl）范围内都显示出出色的活性和稳定性，而且在高温下具有非凡的高稳定性碱性条件（pH 8-10）。bPDT被证明可以熟练地合成许多治疗性核苷，包括去羟肌苷，维达拉滨，克拉屈滨，氟达拉滨和奈拉拉滨。用Ala或Ser进行结构指导的Val11置换，导致变体的活性提高了2.8倍。Tb PDT也共价固定在戊二醛激活的磁性微球上。选择了M Tb PDT3作为最佳衍生物（4200 IU / g，活性回收率为22％），可以轻松地将其重新捕获和再循环用于> 25个反应，而活性损失可忽略不计。最后，男铽PDT3

  DOI：

  10.1002/cctc.201800775

文献信息

• Synthesis of 2-Deoxy-β-D-ribonucleosides and 2,3-Dideoxy-β-D-pentofuranosides on Immobilized Bacterial Cells
  作者：Ivan Votruba、Antonín Holý、Hana Dvořáková、Jaroslav Günter、Dana Hocková、Hubert Hřebabecký、Tomas Cihlar、Milena Masojídková

  DOI：10.1135/cccc19942303

  日期：——

  Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs. All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N⁹-isomers in the purine and N¹-isomers in the pyrimidine series. Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety. The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N⁷-nitrogen atom. On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives. Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed. The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-dideoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-dideoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.

  藻酸盐凝胶包埋的辅助胸腺嘧啶依赖菌株大肠杆菌细胞催化2'-脱氧尿嘧啶的2-脱氧-D-核糖呋喃基团转移到嘌呤和嘧啶碱基以及它们的氮杂和去氮类似物。所有实验都不可避免地产生β-异构体；在大多数情况下，反应是区域特异性的，产生嘌呤中的N⁹-异构体和嘧啶系列中的N¹-异构体。此外，2,3-二脱氧核苷酸可以作为糖基团的供体。嘌呤碱基的受体活性仅在取代上有少许影响，唯一的条件是存在N⁷-氮原子。另一方面，在嘧啶系列中，活性仅限于大多数短链5-烷基和5-卤代尿嘧啶衍生物的狭窄选择。含氨基的杂环碱基会发生脱氨作用；可以通过将碱基转化为相应的N-二甲氨基甲烯基衍生物来避免这种情况，然后进行氨解作用。该方法通过分离腺嘌呤、鸟嘌呤、2-氯腺嘌呤、6-甲基嘌呤、8-氮杂腺嘌呤、8-氮杂鸟嘌呤、1-去氮腺嘌呤、3-去氮腺嘌呤的9-(2-脱氧-β-D-核糖呋喃基)衍生物，5-乙基尿嘧啶、5-氟尿嘧啶的1-(2-脱氧-β-D-核糖呋喃基)衍生物，以及9-(2,3-二脱氧-β-D-戊呋喃基)缺氧嘌呤、9-(2,3-二脱氧-β-D-戊呋喃基)-6-甲基嘌呤和其他核苷酸的验证。
• Mutant purine nucleoside phosphorylase proteins and cellular delivery thereof
  申请人：Ealick E. Steven

  公开号：US20050214901A1

  公开（公告）日：2005-09-29

  A host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside cleavage enzymes is provided. The transformed or transfected host cell can be used in combination with a purine substrate to treat tumour cells and/or virally infected cells. A nucleotide sequence encoding mutant E. coli derived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth is also provided. A method is detailed for the delivery of toxin by generation withing target cells or by administration and delivery to the cells from without. Novel purine nucleosides are detailed that yield a cytotoxic purine upn enzymatic cleavage. A synthetic process for nucleosides is also detailed.

  提供了一种由载有突变嘌呤核苷酸裂解酶编码DNA序列的载体转化或转染的宿主细胞。该转化或转染的宿主细胞可与嘌呤底物结合，用于治疗肿瘤细胞和/或病毒感染的细胞。还提供了编码突变E. coli来源的嘌呤核苷酰化酶蛋白的核苷酸序列，可与适当的底物结合使用，产生有害细胞生长的毒素。详细介绍了一种通过靶细胞内生成或通过外部给药和传递给细胞的毒素递送方法。详细介绍了产生细胞毒性嘌呤核苷酶裂解产物的新型嘌呤核苷。还详细介绍了一种核苷的合成过程。
• MUTANT PURINE NUCLEOSIDE PHOSPHORYLASE PROTEINS AND CELLULAR DELIVERY THEREOF
  申请人：UAB Research Foundation

  公开号：EP1444335A2

  公开（公告）日：2004-08-11
• EP1444335A4
  申请人：——

  公开号：EP1444335A4

  公开（公告）日：2006-03-08
• EP1898956A4
  申请人：——

  公开号：EP1898956A4

  公开（公告）日：2008-07-23