6-硫代肌苷-5'-三磷酸酯 | 27652-34-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 中文名称: 6-硫代肌苷-5'-三磷酸酯
• 英文名称: ({[({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-sulfanyl-9H-purin-9-yl)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid
• 英文别名: 6-thioinosine triphosphate；O^5'-tetrahydroxytriphosphoryl-6-thio-inosine；6-Mercapto-9-β-ribofuranosylpurin-5'-triphosphat(thioITP)；6-Mercapto-9-β-D-ribofuranosylpurin-5'-triphosphat；6-Mercaptopurin-ribosid-5'-triphosphat；6-Thioinosin-5'-triphosphat；[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-sulfanylidene-3H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• CAS: 27652-34-2
• 化学式: C₁₀H₁₅N₄O₁₃P₃S
• 分子量: 524.235
• InChiKey: GQNRDWAOABGWGP-KQYNXXCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  284
• 氢给体数：
  7
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  Guanosine 5'-triphosphate 、 6-硫代肌苷-5'-三磷酸酯 在 human cyclic GMP−AMP synthase 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 反应 16.0h， 生成 2-amino-9-[(1R,6R,8R,9R,10S,15R,17R,18R)-3,9,12,18-tetrahydroxy-3,12-dioxo-8-(6-sulfanylidene-3H-purin-9-yl)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one
  参考文献：
  名称：

  2'-5'，3'-5'-环二核苷酸的酶法制备，它们与干扰素基因衔接子蛋白刺激物的结合特性以及结构/活性相关性。

  摘要：

  环状二核苷酸是环状GMP-AMP合酶（cGAS）-干扰素基因刺激（STING）途径的第二信使，在识别肿瘤细胞和病毒或细菌感染中起着重要作用。它们与STING衔接蛋白结合并通过TANK结合激酶1（TBK1）/干扰素调节因子3（IRF3）和核因子-κB（IκB）激酶（IKK）/核因子-κB（NFκB）抑制剂触发细胞因子的表达信号级联。在这项工作中，我们描述了使用人，小鼠和鸡的环状GMP-AMP合成酶（cGAS）酶法制备2'-5'，3'-5'-环二核苷酸（2'3'CDNs）的方法。我们通过使用一个小的核苷酸5'-三磷酸（NTP）类似物文库来分析这些酶的底物特异性，并使用它们来制备33个2'3'CDN。我们还确定了这些CDN对基于细胞和生化分析的五种不同STING单倍型的亲和力，并描述了它们对所有STING单倍型的最佳活性所需的特性。接下来，我们研究它们对人外周血单核细胞（PBMC）诱导的细胞因子

  DOI：

  10.1021/acs.jmedchem.9b01062
• 作为产物：
  描述：

  6-硫代肌苷 5'-单磷酸酯 在 Meiothermus ruber polyphosphate kinase D₁₂₇S 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 生成 6-硫代肌苷-5'-三磷酸酯 、 3,3'-(十二基亚氨基)二丙烷-1,2-二醇
  参考文献：
  名称：

  10.1002/cctc.202400181

  摘要：

  AbstractPolyphosphate kinases (PPKs) are valuable biocatalysts for ATP cofactor regeneration as well as for the phosphorylation of non‐canonical nucleotides. The versatility of PPKs in the latter application is defined by their substrate scope. In this study, we investigate the substrate spectrum of the PPK2‐III enzyme from Meiothermus ruber (MrPPK) for the conversion of canonical and non‐canonical (deoxy)‐ribonucleotides. The enzyme shows high substrate promiscuity for purine and to minor degree pyrimidine substrates, with an overall preference for the native substrate AMP. With structure guided rational amino acid exchanges in the active site, we produced an MrPPK variant with improved activity for a broad variety of purine nucleotides. While the preference for AMP is lost, conversion of nucleotides without a 6‐amino function at the purine moiety is increased. This MrPPK variant is a versatile biocatalyst for the synthesis of non‐canonical nucleotides and could also be useful as a GTP cofactor regeneration system.

  DOI：

  10.1002/cctc.202400181

文献信息

• Methods of disease activity profiling for personalized therapy management
  申请人：NESTEC S.A.

  公开号：US10086072B2

  公开（公告）日：2018-10-02

  The present invention provides methods for personalized therapeutic management of a disease in order to optimize therapy and/or monitor therapeutic efficacy. In particular, the present invention comprises measuring an array of one or a plurality of biomarkers at a plurality of time points over the course of therapy with a therapeutic agent to determine a mucosal healing index for selecting therapy, optimizing therapy, reducing toxicity, and/or monitoring the efficacy of therapeutic treatment. In certain instances, the therapeutic agent is a TNFα inhibitor for the treatment of a TNFα-mediated disease or disorder.

  本发明提供了对疾病进行个性化治疗管理的方法，以优化治疗和/或监测疗效。特别是，本发明包括在使用治疗剂治疗过程中的多个时间点测量一个或多个生物标志物阵列，以确定用于选择治疗、优化治疗、降低毒性和/或监测疗效的粘膜愈合指数。在某些情况下，治疗剂是 TNFα 抑制剂，用于治疗 TNFα 介导的疾病或紊乱。
• Assays for the detection of anti-TNF drugs and autoantibodies
  申请人：Nestec S.A.

  公开号：US10386366B2

  公开（公告）日：2019-08-20

  The present invention provides assays for detecting and measuring the presence or level of anti-TNFα drug therapeutics and autoantibodies in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNFα drug therapeutics to detect the presence or level of autoantibodies (e.g., HACA and/or HAHA) against the drug.

  本发明提供了用于检测和测量样本中抗 TNFα 药物治疗剂和自身抗体的存在或水平的检测方法。本发明适用于优化治疗和监测接受抗 TNFα 药物治疗的患者，以检测抗药物的自身抗体（如 HACA 和/或 HAHA）的存在或水平。
• Methods for prediction of anti-TNFα drug levels and autoantibody formation
  申请人：Prometheus Biosciences, Inc.

  公开号：US10571467B2

  公开（公告）日：2020-02-25

  In some aspects, the present invention provides methods for predicting whether a subject will develop autoantibodies to an anti-TNFα drug during the course of anti-TNFα drug therapy. In other aspects, the present invention provides methods for predicting the level of an anti-TNFα drug in a subject during the course of anti-TNFα drug therapy. Systems for predicting anti-TNFα drug levels and the likelihood of autoantibody formation during the course of anti-TNFα drug therapy are also provided herein. The present invention further provides methods for predicting a clinical outcome (e.g., endoscopic response) of a subject on anti-TNFα drug therapy.

  在某些方面，本发明提供了在抗TNFα药物治疗过程中预测受试者是否会产生抗TNFα药物自身抗体的方法。在其他方面，本发明提供了在抗TNFα药物治疗过程中预测受试者体内抗TNFα药物水平的方法。本发明还提供了在抗TNFα药物治疗过程中预测抗TNFα药物水平和自身抗体形成可能性的系统。本发明进一步提供了预测抗TNFα药物治疗对象临床结果（如内窥镜反应）的方法。
• Assays for detecting neutralizing autoantibodies to biologic therapy
  申请人：Prometheus Biosciences, Inc.

  公开号：US10794906B2

  公开（公告）日：2020-10-06

  The present invention provides assays for detecting and measuring the presence or level of neutralizing and non-neutralizing autoantibodies to biologics such as anti-TNFα drug therapeutics in a sample. The present invention is useful for monitoring the formation of neutralizing and/or non-neutralizing anti-drug antibodies over time while a subject is on biologic therapy. The present invention is also useful for predicting and/or determining the cross-reactivity of neutralizing anti-drug antibodies in a subject's sample with alternative biologic therapies. As such, the present invention provides information for guiding treatment decisions for those subjects receiving therapy with a biologic agent and improves the accuracy of optimizing therapy, reducing toxicity, and/or monitoring the efficacy of therapeutic treatment to biologic therapy.

  本发明提供了检测和测量样本中生物制剂（如抗肿瘤坏死因子α药物治疗剂）的中和和非中和自身抗体的存在或水平的检测方法。本发明可用于监测受试者在接受生物制剂治疗期间中和和/或非中和抗药物抗体的形成。本发明还可用于预测和/或确定受试者样本中的中和抗药性抗体与替代生物疗法的交叉反应。因此，本发明为那些接受生物制剂治疗的受试者提供了指导治疗决策的信息，并提高了优化治疗、降低毒性和/或监测生物疗法疗效的准确性。
• Blood analysis cartridge
  申请人：King Abdulaziz University

  公开号：US11219895B2

  公开（公告）日：2022-01-11

  A test microfluidic strip or cartridge comprising a blood sample collection zone, red blood cell isolation zone, lysis zone, reagents mixing zone, and sensing zone for measuring the enzymatic activity thiopurine methyltransferase is disclosed. The test strip or cartridge is disclosed to be operably connected to a metering device comprising a processor, a display and a memory card.

  本发明公开了一种测试微流控试剂条或试剂盒，包括血样采集区、红细胞分离区、裂解区、试剂混合区和传感区，用于测量硫嘌呤甲基转移酶的酶活性。据披露，该试纸或试剂盒可操作地连接到一个计量装置上，该装置包括一个处理器、一个显示屏和一个存储卡。