oxythiamine pyrophosphate | 5054-78-4

• 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
• 英文名称: oxythiamine pyrophosphate
• 英文别名: oxyTDP；OTPP；Oxythiamine(1+) pyrophosphate；2-[4-methyl-3-[(2-methyl-6-oxo-1H-pyrimidin-5-yl)methyl]-1,3-thiazol-3-ium-5-yl]ethyl phosphono hydrogen phosphate
• CAS: 5054-78-4
• 化学式: C₁₂H₁₈N₃O₈P₂S
• 分子量: 426.304
• InChiKey: FBFAORFKQFQJGN-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  187
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-[(4-氨基-2-甲基-5-嘧啶基)甲基]-4-甲基-5-[4,6,6-三羟基-4,6-二氧-3,5-二氧-4,6-二磷(五)己-1-基]噻唑-3-鎓 在 盐酸 、 sodium nitrite 、 水 作用下， 以 水 为溶剂， 生成 oxythiamine pyrophosphate
  参考文献：
  名称：

  3-脱氮杂硫胺和氧硫胺酮焦磷酸盐作为丙酮酸脱氢酶复合物抑制剂和体外HeLa细胞生长的效率差异

  摘要：

  摘要 氧胺（OT）和3-脱氮硫胺（DAT）是硫胺的抗代谢物。研究的目的是比较OT和DAT焦磷酸盐（-PP）对哺乳动物丙酮酸脱氢酶复合物（PDHC）动力学和HeLa细胞体外培养的影响。动力学研究表明，3-脱氮杂胺焦磷酸（DATPP）是PDHC的竞争性抑制剂（K i = 0.0026μM）比OTPP（K i = 0.025μM）强得多。两个K i 值都比K m低得多硫胺素焦磷酸（0.06μM）。但是，在HeLa细胞培养的培养基中添加DATPP不会影响细胞的生长速度，并且对细胞的活力没有显着影响，而OTPP和OT则显示出显着的细胞抑制作用。硫胺素类抗维生素在体外对细胞生长的影响上的差异可能是由于理化性质的差异以及DAT跨细胞膜转运的困难。

  DOI：

  10.1080/14756366.2020.1844681

文献信息

• Structural Basis of Thiamine Pyrophosphate Analogues Binding to the Eukaryotic Riboswitch
  作者：Stéphane Thore、Christian Frick、Nenad Ban

  DOI：10.1021/ja801708e

  日期：2008.7.1

  The thiamine pyrophosphate (TPP)-sensing riboswitch is the only riboswitch found in eukaryotes. In plants, TPP regulates its own production by binding to the 3' untranslated region of the mRNA encoding ThiC, a critical enzyme in thiamine biosynthesis, which promotes the formation of an unstable splicing variant. In order to better understand the molecular basis of TPP-analogue binding to the eukaryotic TPP-responsive riboswitch, we have determined the crystal structures of the Arabidopsis thaliana TPP-riboswitch in complex with oxythiamine pyrophosphate (OTPP) and with the antimicrobial compound pyrithiamine pyrophosphate (PTPP). The OTPP-riboswitch complex reveals that the pyrimidine ring of OTPP is stabilized in its enol form in order to retain key interactions with guanosine 28 of the riboswitch previously observed in the TPP complex. The structure of PTPP in complex with the riboswitch shows that the base moiety of guanosine 60 undergoes a conformational change to cradle the pyridine ring of the PTPP. Structural information from these complexes has implications for the design of novel antimicrobials targeting TPP-sensing riboswitches.
• Differences in the efficiency of 3-deazathiamine and oxythiamine pyrophosphates as inhibitors of pyruvate dehydrogenase complex and growth of HeLa cells <i>in vitro</i>
  作者：Ewa Grabowska、Magdalena Czerniecka、Urszula Czyżewska、Aneta Zambrzycka、Zenon Łotowski、Adam Tylicki

  DOI：10.1080/14756366.2020.1844681

  日期：2021.1.1

  Abstract Oxythiamine (OT) and 3-deazathiamine (DAT) are the antimetabolites of thiamine. The aim of study was to compare the effects of OT and DAT pyrophosphates (-PP) on the kinetics of mammalian pyruvate dehydrogenase complex (PDHC) and the in vitro culture of HeLa cells. The kinetic study showed that 3-deazathiamine pyrophosphate (DATPP) was a much stronger competitive inhibitor (Ki = 0.0026 μM)

  摘要 氧胺（OT）和3-脱氮硫胺（DAT）是硫胺的抗代谢物。研究的目的是比较OT和DAT焦磷酸盐（-PP）对哺乳动物丙酮酸脱氢酶复合物（PDHC）动力学和HeLa细胞体外培养的影响。动力学研究表明，3-脱氮杂胺焦磷酸（DATPP）是PDHC的竞争性抑制剂（K i = 0.0026μM）比OTPP（K i = 0.025μM）强得多。两个K i 值都比K m低得多硫胺素焦磷酸（0.06μM）。但是，在HeLa细胞培养的培养基中添加DATPP不会影响细胞的生长速度，并且对细胞的活力没有显着影响，而OTPP和OT则显示出显着的细胞抑制作用。硫胺素类抗维生素在体外对细胞生长的影响上的差异可能是由于理化性质的差异以及DAT跨细胞膜转运的困难。