[(2S,3S,5S)-3-叠氮基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基膦酰磷酸氢酯 | 106060-89-3

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机含氧阴离子化合物
• 中文名称: [(2S,3S,5S)-3-叠氮基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基膦酰磷酸氢酯
• 英文名称: 3'-azido-2',3'-dideoxythymidine 5'-diphosphate
• 英文别名: 3'-azido-3'-deoxythymidine-5'-O-diphosphate；3'-azido-3'-deoxythymidine 5'-diphosphate；3'-azido-3'-deoxythymidine-5'-diphosphate；3'-azido-3'-deoxythymidine diphosphate；zidovudine diphosphate；AZT 5'-diphosphate；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate
• CAS: 106060-89-3
• 化学式: C₁₀H₁₅N₅O₁₀P₂
• 分子量: 427.204
• InChiKey: QOYVAFWJURKBJG-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  186
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [α-32P]ATP 、 [(2S,3S,5S)-3-叠氮基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基膦酰磷酸氢酯 在 amino acid mixture 三羟甲基氨基甲烷盐酸盐 、 Escherichia coli inorganic pyrophosphatase 作用下， 以 水 为溶剂， 反应 0.25h， 生成 、 、
  参考文献：
  名称：

  [双（5'-核苷）四或三磷酸的酶促合成]。

  摘要：

  已显示，来自大肠杆菌的氨酰基-tRNA合成酶的总级分催化由（alpha-32P）合成双（5'-核苷）低聚磷酸盐Ap4AZT，Ap4d4T，Ap43TC和Ap4ACV，以及Ap3AZT和Ap3d4T。 ATP和相应的5'-三（或二）磷酸核苷。通过HPLC表征的所得化合物对碱性磷酸酶具有抗性。Ap4AZT，Ap4d4T和Ap43TC的形成效率大致相等，而Ap4ACV，Ap3AZT和Ap3d4T的合成效率要低三到五倍。该论文的英文版：Russian Journal of Bioorganic Chemistry，2005年，第1卷。31号 6; 另请参见http://www.maik.ru。

  DOI：

  10.1007/s11171-005-0077-6
• 作为产物：
  描述：

  齐多夫定 在 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 、 三正丁胺 、 triethylammonium carbonate buffer 、 tetrabutylammonium phosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 以22%的产率得到[(2S,3S,5S)-3-叠氮基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基膦酰磷酸氢酯
  参考文献：
  名称：

  双位受体锌（II）-双（循环）配合物（Cyclen = 1,4,7,10-四氮杂环十二烷）对水溶液中胸苷单磷酸和二磷酸核苷酸的高度选择性识别

  摘要：

  高度选择性和高效地识别胸苷和尿苷核苷酸，例如 3'-dTMP（胸苷 3'-单磷酸）、5'-dTMP（胸苷 5'-单磷酸）、2'-UMP（尿苷 2'-单磷酸）、3' -UMP（尿苷 3'-单磷酸）、5'-UMP（尿苷 5'-单磷酸）、5'-dTDP（胸苷 5'-二磷酸）、5'-dTTP（胸苷 5'-三磷酸）、AZTMP（3'） -叠氮基-3'-脱氧胸苷 5'-单磷酸酯）和 AZTDP（3'-叠氮基-3'-脱氧胸苷 5'-二磷酸酯）与大环 12 元四胺、间位和对位的双位二聚锌 (II) 复合物已经通过电位 pH 滴定、等温滴定量热法、紫外分光光度法滴定和 NMR 滴定对二甲苯基-双 (Zn2+-cyclen)s（Zn2L4 和 Zn2L5）（cyclen = 1,4,7,10-四氮杂环十二烷）进行了研究。5'-dTMP 的表观 1:1 络合常数，

  DOI：

  10.1021/ja994537s

文献信息

• The Structure of Thymidylate Kinase from <i>Candida albicans</i> Reveals a Unique Structural Element
  作者：Kaustubh Sinha、Gordon S. Rule

  DOI：10.1021/acs.biochem.7b00498

  日期：2017.8.22

  The structure of thymidylate kinase from Candida albicans, determined by X-ray crystallography, is reported to a resolution of 2.45 Å with a final Rfree of 0.223. Thymidylate kinase from C. albicans possesses a unique 15-residue loop that is not seen in thymidylate kinases from other genera. The structure reported here reveals that the conformation of this loop is constrained by both intra- and intersubunit hydrogen bonding, and a number of key residues in this loop are conserved among different Candida species that are medically important. The substrate specificity of the enzyme was determined using a novel nuclear magnetic resonance-based assay as well as a traditional coupled assay. The enzyme is active against 3′-azido-3′-deoxythymidine monophosphate and moderately active with dGMP. The distinct functional and structural differences between the C. albicans enzyme and the human enzyme suggest that thymidylate kinase is an appropriate target for the development of new antifungal agents.

  据报道，白色念珠菌胸苷酸激酶的结构通过 X 射线晶体学测定，分辨率为 2.45 Å，最终 Rfree 为 0.223。来自白色念珠菌的胸苷酸激酶具有独特的 15 个残基环，这在其他属的胸苷酸激酶中是不存在的。这里报告的结构表明，该环的构象受到亚基内和亚基间氢键的约束，并且该环中的许多关键残基在医学上重要的不同念珠菌物种之间是保守的。使用基于核磁共振的新型测定以及传统的偶联测定来确定酶的底物特异性。该酶对 3'-叠氮基-3'-脱氧胸苷单磷酸具有活性，对 dGMP 具有中等活性。白色念珠菌酶和人类酶之间明显的功能和结构差异表明胸苷酸激酶是开发新抗真菌剂的合适靶标。
• MODIFIED OLIGONUCLEOTIDES CONTAINING DIPHOSPHODIESTER INTERNUCLEOTIDE LINKAGES
  申请人：Parang Keykavous

  公开号：US20080207551A1

  公开（公告）日：2008-08-28

  The synthesis and biochemical utility of modified oligonucleotides containing diphosphodiester internucleotide linkages. The synthesis of these compounds was carried out using diphosphitylating reagents. Oligonucleotides containing diphosphate diester bridges wherein said oligonucleotides are synthesized via a solid-phase synthesis strategy to form modified oligonucleotides. Diphosphitylating, triphosphitylating, tetraphosphitylating, β-triphosphitylating, bifunctional diphosphitylating, bifunctional triphosphitylating, and bifunctional tetraphosphitylating reagents wherein, the phosphorus atoms are linked together through oxygen, sulfur, amino, or methylene groups and/or are substituted with chlorine, diisopropylamine and cyanoethoxy groups.

  含有二磷酸二酯间核苷酸连接的修饰寡核苷酸的合成和生物化学应用。这些化合物的合成是使用二磷酸化试剂进行的。通过固相合成策略合成含有二磷酸二酯桥的寡核苷酸来形成修饰寡核苷酸。其中，二磷酸化、三磷酸化、四磷酸化、β-三磷酸化、双官能团二磷酸化、双官能团三磷酸化和双官能团四磷酸化试剂中的磷原子通过氧、硫、氨基或亚甲基基团连接在一起，并且/或被氯、二异丙基胺和氰乙氧基基团取代。
• Lipid derivatives of antiviral nucleosides, liposomal incorporation and method of use
  申请人：NeXstar Pharmaceuticals, Inc.

  公开号：EP0350287A2

  公开（公告）日：1990-01-10

  Compounds are disclosed for treating AIDS, herpes, and other viral infections by means of lipid derivatives of antiviral agents. The compounds consist of nucleoside analogues having antiviral activity which are linked, commonly through a phosphate group at the 5′ position of the pentose residue, to one of a selected group of lipids. The lipophilic nature of these compounds provide advantages over the use of the nucleoside analogue alone. It also makes it possible to incorporate them into the lamellar structure of liposomes, either alone or combined with similar molecules. In the form of liposomes, these antiviral agents are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target HIV virus. Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins. Effective nucleoside analogues are dideoxynucleosides, azidothymine (AZT), and acyclovir; lipid groups may be glycolipids, sphingolipids, phospholipids or fatty acids. The compounds persist, after intracellular hydrolysis, as phosphorylated or non-phosphorylated antiviral nucleosides. The compounds are effective in improving the efficacy of antiviral nucleoside analogues by prolonging the antiviral activity after the administration of the drug has ended, and in preventing retroviral replication in HIV infections which have become resistant to therapy with conventional forms of the antiretroviral agents.

  公开了通过抗病毒剂的脂质衍生物治疗艾滋病、疱疹和其他病毒感染的化合物。这些化合物由具有抗病毒活性的核苷类似物组成，核苷类似物通常通过戊糖残基 5′位上的磷酸基团与一组选定的脂质中的一种相连接。与单独使用核苷类似物相比，这些化合物的亲脂性更具优势。这也使得它们可以单独或与类似分子结合，加入脂质体的片层结构中。在脂质体的形式下，这些抗病毒药物会优先被巨噬细胞和单核细胞吸收，而这些细胞已被发现携带目标 HIV 病毒。在脂质体中加入配体，如与病毒蛋白结合的单克隆抗体或其他肽或蛋白质，还可增加作用点的特异性。有效的核苷类似物有双脱氧核苷、叠氮胸苷（AZT）和阿昔洛韦；脂质基团可以是糖脂、鞘磷脂、磷脂或脂肪酸。这些化合物在细胞内水解后，以磷酸化或非磷酸化的抗病毒核苷形式存在。这些化合物可在给药结束后延长抗病毒活性，从而有效改善抗病毒核苷类似物的疗效，并可在对传统形式的抗逆转录病毒药物治疗产生耐药性的艾滋病毒感染中防止逆转录病毒复制。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• Methods of treating viral infections using antiviral liponucleotides
  申请人：——

  公开号：US20010033862A1

  公开（公告）日：2001-10-25

  Compounds are disclosed for treating AIDS, herpes, and other viral infections by means of lipid derivatives of antiviral agents. The compounds consist of nucleoside analogues having antiviral activity which are linked, commonly through a phosphate group at the 5′ position of the pentose residue, to one of a selected group of lipids. The lipophilic nature of these compounds provide advantages over the use of the nucleoside analogue alone. It also makes it possible to incorporate them into the lamellar structure of liposomes, either alone or combined with similar molecules. In the form of liposomes, these antiviral agents are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target HIV virus. Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins. Effective nucleoside analogues are dideoxynucleosides, azidothymine (AZT), and acyclovir; lipid groups may be glycolipids, sphingolipids, phospholipids or fatty acids. The compounds persist, after intracellular hydrolysis, as phosphorylated or non-phosphorylated antiviral nucleosides. The compounds are effective in improving the efficacy of antiviral nucleoside analogues by prolonging the antiviral activity after the administration of the drug has ended, and in preventing retroviral replication in HIV infections which have become resistant to therapy with conventional forms of the antiretroviral agents.

  公开了通过抗病毒剂的脂质衍生物治疗艾滋病、疱疹和其他病毒感染的化合物。这些化合物由具有抗病毒活性的核苷类似物组成，核苷类似物通常通过戊糖残基 5′位上的磷酸基团与一组选定的脂质中的一种相连接。与单独使用核苷类似物相比，这些化合物的亲脂性更具优势。这也使得它们可以单独或与类似分子结合，加入脂质体的片层结构中。在脂质体的形式下，这些抗病毒药物会优先被巨噬细胞和单核细胞吸收，而这些细胞已被发现携带目标 HIV 病毒。在脂质体中加入配体，如与病毒蛋白结合的单克隆抗体或其他肽或蛋白质，还可增加作用点的特异性。有效的核苷类似物有双脱氧核苷、叠氮胸苷（AZT）和阿昔洛韦；脂质基团可以是糖脂、鞘磷脂、磷脂或脂肪酸。这些化合物在细胞内水解后，以磷酸化或非磷酸化的抗病毒核苷形式存在。这些化合物可在给药结束后延长抗病毒活性，从而有效改善抗病毒核苷类似物的疗效，并可在对传统形式的抗逆转录病毒药物治疗产生耐药性的艾滋病毒感染中防止逆转录病毒复制。