2-甲硫基-N-6-异戊烯基腺苷 | 20859-00-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2-甲硫基-N-6-异戊烯基腺苷
• 英文名称: 2-methylthio-N6-isopentenyladenosine
• 英文别名: 2-methylthio-iPR；S-methyl-N⁶-(3-methyl-but-2-enyl)-2-thio-isoguanosine；6-(3-Methyl-2-butenylamino)-2-methylthio-9-β-D-ribofuranosylpurin；2-Methylthio-N⁶-(Δ²-isopentenyl)-adenosin；Nucleosid；2-Methylthio-N-6-isopentenyladenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-(3-methylbut-2-enylamino)-2-methylsulfanylpurin-9-yl]oxolane-3,4-diol
• CAS: 20859-00-1
• 化学式: C₁₆H₂₃N₅O₄S
• 分子量: 381.456
• InChiKey: VZQXUWKZDSEQRR-SDBHATRESA-N

物化性质

• 溶解度：
  soluble in No data available

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  151
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-甲硫基-N-6-异戊烯基腺苷 在 Salmonella typhimurium O₂-dependent tRNA modifying monooxgenase 、 双氧水 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成 N⁶-(4-hydroxy-3-methyl-but-2-enyl)-S-methyl-2-thio-isoguanosine
  参考文献：
  名称：

  Peroxide-Shunt Substrate-Specificity for the Salmonella typhimurium O₂-Dependent tRNA Modifying Monooxygenase (MiaE)

  摘要：

  Post-transcriptional modifications of tRNA are made to structurally diversify tRNA. These modifications alter noncovalent interactions within the ribosomal machinery, resulting in phenotypic changes related to cell metabolism, growth, and virulence. MiaE is a carboxylate bridged, nonheme diiron monooxygenase, which catalyzes the O-2-dependent hydroxylation of a hypermodified-tRNA nucleoside at position 37 (2-methylthio-N-6-isopentenyl-adenosine(37)-tRNA) [designated ms(2)i(6)A(37)]. In this work, recombinant MiaE was cloned from Salmonella typhimurium, purified to homogeneity, and characterized by UV-visible and dual-mode X-band EPR spectroscopy for comparison to other nonheme diiron enzymes. Additionally, three nucleoside substrate-surrogates (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) and their corresponding hydroxylated products (io(6)A, Cl(2)io(6)A, and ms(2)io(6)A) were synthesized to investigate the chemo- and stereospecificity of this enzyme. In the absence of the native electron transport chain, the peroxide-shunt was utilized to monitor the rate of substrate hydroxylation. Remarkably, regardless of the substrate (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) used in peroxide-shunt assays, hydroxylation of the terminal isopentenyl-C4-position was observed with >97% E-stereoselectivity. No other nonspecific hydroxylation products were observed in enzymatic assays. Steady-state kinetic experiments also demonstrate that the initial rate of MiaE hydroxylation is highly influenced by the substituent at the C2-position of the nucleoside base (v(0)/[E] for ms(2)i(6)A > i(6)A > Cl(2)i(6)A). Indeed, the >3-fold rate enhancement exhibited by MiaE for the hydroxylation of the free ms(2)i(6)A nucleoside relative to i(6)A is consistent with previous whole cell assays reporting the ms(2)io(6)A and io(6)A product distribution within native tRNA-substrates. This observation suggests that the nucleoside C2-substituent is a key point of interaction regulating MiaE substrate specificity:

  DOI：

  10.1021/bi4000832
• 作为产物：
  描述：

  3-甲基-2-丁烯-1-胺盐酸盐(1:1) 在 甲醇 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 、 potassium carbonate 作用下， 以 乙腈 、 正丁醇 为溶剂， 反应 29.0h， 生成 2-甲硫基-N-6-异戊烯基腺苷
  参考文献：
  名称：

  Peroxide-Shunt Substrate-Specificity for the Salmonella typhimurium O₂-Dependent tRNA Modifying Monooxygenase (MiaE)

  摘要：

  Post-transcriptional modifications of tRNA are made to structurally diversify tRNA. These modifications alter noncovalent interactions within the ribosomal machinery, resulting in phenotypic changes related to cell metabolism, growth, and virulence. MiaE is a carboxylate bridged, nonheme diiron monooxygenase, which catalyzes the O-2-dependent hydroxylation of a hypermodified-tRNA nucleoside at position 37 (2-methylthio-N-6-isopentenyl-adenosine(37)-tRNA) [designated ms(2)i(6)A(37)]. In this work, recombinant MiaE was cloned from Salmonella typhimurium, purified to homogeneity, and characterized by UV-visible and dual-mode X-band EPR spectroscopy for comparison to other nonheme diiron enzymes. Additionally, three nucleoside substrate-surrogates (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) and their corresponding hydroxylated products (io(6)A, Cl(2)io(6)A, and ms(2)io(6)A) were synthesized to investigate the chemo- and stereospecificity of this enzyme. In the absence of the native electron transport chain, the peroxide-shunt was utilized to monitor the rate of substrate hydroxylation. Remarkably, regardless of the substrate (i(6)A, Cl(2)i(6)A, and ms(2)i(6)A) used in peroxide-shunt assays, hydroxylation of the terminal isopentenyl-C4-position was observed with >97% E-stereoselectivity. No other nonspecific hydroxylation products were observed in enzymatic assays. Steady-state kinetic experiments also demonstrate that the initial rate of MiaE hydroxylation is highly influenced by the substituent at the C2-position of the nucleoside base (v(0)/[E] for ms(2)i(6)A > i(6)A > Cl(2)i(6)A). Indeed, the >3-fold rate enhancement exhibited by MiaE for the hydroxylation of the free ms(2)i(6)A nucleoside relative to i(6)A is consistent with previous whole cell assays reporting the ms(2)io(6)A and io(6)A product distribution within native tRNA-substrates. This observation suggests that the nucleoside C2-substituent is a key point of interaction regulating MiaE substrate specificity:

  DOI：

  10.1021/bi4000832

文献信息

• The Transcriptome-Wide Mapping of 2-Methylthio-<i>N</i>⁶-isopentenyladenosine at Single-Base Resolution
  作者：Zhentian Fang、Ziang Lu、Shaoqing Han、Yuanyuan Zhou、Wei Yang、Xiaolian Zhang、Xiang Zhou

  DOI：10.1021/jacs.2c13894

  日期：2023.3.8

  A transcriptome-wide and single-base resolution method that enables absolute mapping of ms2i6A along with analysis of its distribution in different RNAs is lacking. Here, through chemoselective methylthio group bioconjugation, we introduce a new approach (redox activated chemical tagging sequencing, ReACT-seq) to detect ms2i6A transcriptome-wide at single-base resolution. Using the chemoselectivity

  已鉴定出数百个修饰碱基并进行酶促修饰以转移 RNA (tRNA) 以调节各种生物体中的 RNA 功能。2-甲硫基-N 6 -异戊烯基腺苷 (ms 2 i 6 A) 是一种在 tRNA 第 37 位发现的超修饰碱基，存在于原核生物和真核生物中。ms 2 i 6 A 传统上是通过使用 RNA 质谱法从总 RNA 中分离和消化每个 tRNA 来识别的。一种全转录组和单碱基分辨率方法，可实现 ms 2 i 6的绝对映射缺乏对其在不同 RNA 中分布的分析。在这里，通过化学选择性甲硫基生物偶联，我们引入了一种新方法（还原激活化学标记测序，ReACT-seq ）以单碱基分辨率检测全转录组 ms 2 i 6 A。利用甲硫基和氧氮丙啶基团之间的化学选择性，ms 2 i 6A 用叠氮基进行生物正交标记，不受规范核苷酸的干扰，从而在测序前促进甲硫基修饰的 RNA 的富集。ReACT-seq 在九个已知的 tRNA
• MR1 LIGANDS AND PHARMACEUTICAL COMPOSITIONS FOR IMMUNOMODULATION
  申请人：Universität Basel

  公开号：EP3889602A1

  公开（公告）日：2021-10-06

  The invention relates to a method for modulating an interaction between an MR1 polypeptide and an MR1-specific T cell receptor molecule, whereby a MR1 polypeptide is contacted with a MR1 ligand compound that is a nucleobase adduct product reflecting a state of metabolic distress of a eukaryotic cell. The invention further relates to the use of compounds identified as MR1 ligands in vaccination or modulation of an MR1-restricted immune response.

  本发明涉及一种调节MR1多肽与MR1特异性T细胞受体分子之间相互作用的方法，其中MR1多肽与MR1配体化合物接触，MR1配体化合物是反映真核细胞代谢窘迫状态的核碱基加合物产物。 本发明进一步涉及鉴定为 MR1 配体的化合物在疫苗接种或调节 MR1 限制性免疫反应中的用途。
• Recombinant nucleoside-specific ribonuclease and method of producing and using same
  申请人：University of Cincinnati

  公开号：US11535834B2

  公开（公告）日：2022-12-27

  A recombinant ribonuclease is disclosed. The recombinant ribonuclease is produced by introducing a recombinant DNA sequence into a host; activating expression of the recombinant DNA sequence within the host to produce the recombinant ribonuclease; and isolating the recombinant ribonuclease from the host. Additionally, a method of analyzing an RNA sequence includes digesting the RNA with a first recombinant ribonuclease to give digestion products comprising nucleotides of the RNA sequence; and analyzing the digestion products using an analytical method to provide the identity of at least some of the nucleotides. The recombinant ribonuclease includes at least one of a uridine-specific recombinant RNase MC1 and a cytidine-specific recombinant RNase Cusativin.

  本发明公开了一种重组核糖核酸酶。重组核糖核酸酶是通过以下方法产生的：将重组 DNA 序列导入宿主；激活宿主内重组 DNA 序列的表达以产生重组核糖核酸酶；以及从宿主中分离重组核糖核酸酶。此外，一种分析 RNA 序列的方法包括用第一种重组核糖核酸酶消化 RNA，以得到包含 RNA 序列核苷酸的消化产物；以及使用分析方法分析消化产物，以提供至少部分核苷酸的特性。重组核糖核酸酶包括尿苷特异性重组 RNase MC1 和胞苷特异性重组 RNase Cusativin 中的至少一种。
• RECOMBINANT NUCLEOTIDE-SPECIFIC RIBONUCLEASE AND METHOD OF PRODUCING AND USING SAME
  申请人：University of Cincinnati

  公开号：EP3286305A2

  公开（公告）日：2018-02-28
• RECOMBINANT NUCLEOSIDE-SPECIFIC RIBONUCLEASE AND METHOD OF PRODUCING AND USING SAME
  申请人：University Of Cincinnati

  公开号：US20180320154A1

  公开（公告）日：2018-11-08

  A recombinant ribonuclease is disclosed. The recombinant ribonuclease is produced by introducing a recombinant DNA sequence into a host; activating expression of the recombinant DNA sequence within the host to produce the recombinant ribonuclease; and isolating the recombinant ribonuclease from the host. Additionally, a method of analyzing an RNA sequence includes digesting the RNA with a first recombinant ribonuclease to give digestion products comprising nucleotides of the RNA sequence; and analyzing the digestion products using an analytical method to provide the identity of at least some of the nucleotides. The recombinant ribonuclease includes at least one of a uridine-specific recombinant RNase MC1 and a cytidine-specific recombinant RNase Cusativin.