thG | 1333168-10-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: thG
• 英文别名: 2-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H-thieno[3,4-d]pyrimidin-4-one
• CAS: 1333168-10-7
• 化学式: C₁₁H₁₃N₃O₅S
• 分子量: 299.307
• InChiKey: QSDNXCAUOGNHNI-XVFCMESISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  166
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  thG 在 高氯酸 、 氨基磺酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成
  参考文献：
  名称：

  开启荧光/ FRET探针，以研究人组氨酸三联体核苷酸结合蛋白1（hHint1），这是阿片类药物耐受和神经性疼痛的新靶点†

  摘要：

  组氨酸三联体核苷酸结合蛋白1（Hint1）已成为重要的突触后蛋白，与多种中枢神经系统疾病（如疼痛，成瘾和精神分裂症）相关。最近，用一种小的核苷抑制剂抑制组氨酸核苷酸结合蛋白1（Hint1）已显示出有望作为治疗神经性疼痛的一种新的治疗策略。在这里，我们描述了第一个合理设计的具有双重荧光和FRET特性的小分子开关探针，以研究Hint1。通过连接子将两个荧光寿命分别为20和25 ns的非天然荧光核苷与吲哚环偶联，即探针7和8。发现这两种探针都是水溶性的，并且通过光致电子转移（PET）在分子内淬灭，导致背景荧光最小。与Hint1孵育后，化合物7和8的荧光强度与对照相比分别提高了40倍和16倍。化合物7和8分别以0.121±0.02和2.2±0.36μM的解离常数结合Hint1。我们证明了探针8表现出具有活性位点色氨酸残基（W123）的FRET接通特性。我们展示了探针在进行定量配体置换研究以及细胞裂

  DOI：

  10.1039/c7ob02472j
• 作为产物：
  描述：

  在 氨 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 thG
  参考文献：
  名称：

  开启荧光/ FRET探针，以研究人组氨酸三联体核苷酸结合蛋白1（hHint1），这是阿片类药物耐受和神经性疼痛的新靶点†

  摘要：

  组氨酸三联体核苷酸结合蛋白1（Hint1）已成为重要的突触后蛋白，与多种中枢神经系统疾病（如疼痛，成瘾和精神分裂症）相关。最近，用一种小的核苷抑制剂抑制组氨酸核苷酸结合蛋白1（Hint1）已显示出有望作为治疗神经性疼痛的一种新的治疗策略。在这里，我们描述了第一个合理设计的具有双重荧光和FRET特性的小分子开关探针，以研究Hint1。通过连接子将两个荧光寿命分别为20和25 ns的非天然荧光核苷与吲哚环偶联，即探针7和8。发现这两种探针都是水溶性的，并且通过光致电子转移（PET）在分子内淬灭，导致背景荧光最小。与Hint1孵育后，化合物7和8的荧光强度与对照相比分别提高了40倍和16倍。化合物7和8分别以0.121±0.02和2.2±0.36μM的解离常数结合Hint1。我们证明了探针8表现出具有活性位点色氨酸残基（W123）的FRET接通特性。我们展示了探针在进行定量配体置换研究以及细胞裂

  DOI：

  10.1039/c7ob02472j

文献信息

• Cellular activity of siRNA oligonucleotides containing synthetic isomorphic nucleoside surrogates
  作者：Dongwon Shin、Peter Lönn、Steven F. Dowdy、Yitzhak Tor

  DOI：10.1039/c4cc08809c

  日期：——

  Singly and multiply modified synthetic siRNA oligonucleotides, containing highly isomorphic surrogate nucleobases, show high interference activity in cell culture.

  含高同构代用核碱基的单个和多个修饰的合成siRNA寡核苷酸，在细胞培养中表现出高的干扰活性。
• Emissive RNA Alphabet
  作者：Dongwon Shin、Renatus W. Sinkeldam、Yitzhak Tor

  DOI：10.1021/ja206095a

  日期：2011.9.28

  A fluorescent ribonucleoside alphabet consisting of highly emissive purine ((th)A, (th)G) and pyrimidine (U-th, C-th) analogues, all derived from thieno[3,4-d]pyrimidine as the heterocyclic nucleus, is described. Structural and biophysical analyses demonstrated that the emissive analogues are faithful isomorphic nucleoside surrogates. Photophysical analysis established that the nucleosides offer highly desirable qualities, including visible emission, high quantum yield, and responsiveness to environmental perturbations, traits entirely lacking in their native counterparts.
• Isomorphic Emissive GTP Surrogate Facilitates Initiation and Elongation of in Vitro Transcription Reactions
  作者：Lisa S. McCoy、Dongwon Shin、Yitzhak Tor

  DOI：10.1021/ja5039227

  日期：2014.10.29

  The fastidious behavior of T7 RNA polymerase limits the incorporation of synthetic nucleosides into RNA transcripts, particularly at or near the promoter. The practically exclusive use of GTP for transcription initiation further compounds this challenge, and reactions with GTP analogs, where the heterocyclic nucleus has been altered, have not, to our knowledge, been demonstrated. The enzymatic incorporation of (th)GTP, a newly synthesized isomorphic fluorescent nucleotide with a thieno[3,4-d]pyrimidine core, is explored. The modified nucleotide can initiate and maintain transcription reactions, leading to the formation of fully modified and highly emissive RNA transcripts with (th)G replacing all guanosine residues. Short and long modified transcripts are synthesized in comparable yields to their natural counterparts. To assess proper folding and function, transcripts were used to assemble a hammerhead ribozyme with all permutations of natural and modified enzyme and substrate strands. The (th)G modified substrate was effectively cleaved by the natural RNA enzyme, demonstrating the isomorphic features of the nucleoside and its ability to replace G residues while retaining proper folding. In contrast, the (th)G modified enzyme showed little cleavage ability, suggesting the modifications likely disrupted the catalytic center, illustrating the significance of the Hoogsteen face in mediating appropriate contacts. Importantly, the ribozyme cleavage reaction of the emissive fluorescent transcripts could be followed in real time by fluorescence spectroscopy. Beyond their utility as fluorescent probes in biophysical and discovery assays, the results reported point to the potential utility of such isomorphic nucleosides in probing specific mechanistic questions in RNA catalysis and RNA structural analysis.
• Emissive Guanosine Analog Applicable for Real-Time Live Cell Imaging
  作者：Kfir B. Steinbuch、Deyuan Cong、Anthony J. Rodriguez、Yitzhak Tor

  DOI：10.1021/acschembio.4c00398

  日期：2024.8.16