uridine 5'-(tetrahydrogen triphosphate) | 23198-01-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: uridine 5'-(tetrahydrogen triphosphate)
• 英文别名: 5-methyluridine 5'-triphosphate；ribothymidine triphosphate；thymidine triphosphate；5-methyl-UTP；TTP；UTP；[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• CAS: 23198-01-8
• 化学式: C₁₀H₁₇N₂O₁₅P₃
• 分子量: 498.171
• InChiKey: RZCIEJXAILMSQK-JXOAFFINSA-N

物化性质

• 密度：
  2.010±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  259
• 氢给体数：
  7
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  卡那霉素碱 、 uridine 5'-(tetrahydrogen triphosphate) 在 DL-dithiothreitol 、 aminoglycoside nucleotidyltransferase from staphylococcus aureus 、 potassium chloride 、 magnesium chloride 作用下， 生成
  参考文献：
  名称：

  Dissecting the cosubstrate structure requirements of the Staphylococcus aureus aminoglycoside resistance enzyme ANT(4′)

  摘要：

  Aminoglycosides are important antibiotics used against a wide range of pathogens. As a mechanism of defense, bacteria have evolved enzymes able to inactivate these drugs by regio-selectively adding a variety of functionalities (acetyl, phospho, and nucelotidyl groups) to their scaffolds. The aminoglycoside nucleotidyltransferase ANT(4') is one of the most prevalent and unique modifying-enzymes. Here, by TLC, HRMS, and colorimetric assays, we demonstrate that the resistance enzyme ANT(4') from Staphylococcus aureus is highly substrate and cosubstrate promiscuous. We show that deoxy-ribonucleotide triphosphates (dNTPs) are better cosubstrates than NTPs. We demonstrate that the position of the triphosphate group (5' and not 3') on the ribose/deoxyribose ring is important for recognition by ANT(4'), and that NTPs with larger substituents at the 3'-position of the ribose ring are not cosubstrates for ANT(4'). We confirm that for all aminoglycosides tested, the respective nucleotidylated products are completely inactive. These results provide valuable insights into the development of strategies to combat the ever-growing bacterial resistance problem. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bbrc.2010.10.119
• 作为产物：
  描述：

  Thymidin-5'-monophosphat 在 Meiothermus ruber polyphosphate kinase wild type 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 生成 TDP 、 uridine 5'-(tetrahydrogen triphosphate)
  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

• POLY(PHOSPHOESTERS) FOR DELIVERY OF NUCLEIC ACIDS
  申请人：TRANSLATE BIO, INC.

  公开号：US20200277446A1

  公开（公告）日：2020-09-03

  Disclosed are polymers comprising the moiety A, which is a moiety of formula I: and pharmaceutically acceptable salts thereof, wherein R, R 1 , R 2 , L, n1 and n2 are as defined herein. These polymers are useful for delivering nucleic acids to subject. These polymers and pharmaceutically acceptable compositions comprising such polymers and nucleic acids can be useful for treating various diseases, disorders and conditions.

  揭示了包含A基团的聚合物，该基团是化学式I的基团：及其药用可接受的盐，其中R、R1、R2、L、n1和n2如本文所定义。这些聚合物对于将核酸传递给受试者是有用的。这些聚合物和包含这些聚合物和核酸的药用可接受组合物可用于治疗各种疾病、疾病和症状。
• [EN] COMPOSITIONS AND METHODS FOR SYNTHESIS OF PHOSPHORYLATED MOLECULES<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE DE MOLÉCULES PHOSPHORYLÉES
  申请人：UNIV CALIFORNIA

  公开号：WO2019195494A1

  公开（公告）日：2019-10-10

  The invention provides compositions and methods for synthesis of phosphorylated organic compounds, including nucleoside triphosphates.

  这项发明提供了合成磷酸化有机化合物的组合物和方法，包括核苷三磷酸。
• [EN] CATIONIC LIPIDS COMPRISING AN HYDROXY MOIETY<br/>[FR] LIPIDES CATIONIQUES COMPRENANT UNE FRACTION HYDROXY
  申请人：TRANSLATE BIO INC

  公开号：WO2020257611A1

  公开（公告）日：2020-12-24

  Disclosed are lipids which are compounds of Formula I. Lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

  本文披露的是化合物I的脂质。本文提供的脂质可用于传递和表达mRNA和编码蛋白，例如作为脂质体传递载体的组分，因此可用于治疗与一种或多种蛋白质缺乏相关的各种疾病、紊乱和症状。
• [EN] LIPIDIC COMPOUNDS COMPRISING AT LEAST ONE TERMINAL RADICAL OF FORMULA -NH-CX-A OR -NH-CX-NH-A, COMPOSITIONS CONTAINING THEM AND USES THEREOF<br/>[FR] COMPOSÉS LIPIDIQUES COMPRENANT AU MOINS UN RADICAL TERMINAL DE FORMULE -NH-CX-A OU -NH-CX-NH-A, COMPOSITIONS LES CONTENANT ET LEURS UTILISATIONS
  申请人：SANOFI PASTEUR

  公开号：WO2022013443A1

  公开（公告）日：2022-01-20

  The disclosure relates to novel lipidic compounds, lipid nanoparticles (LNPs) containing thereof, and the use of the lipidic compounds or the LNPs for the delivery of nucleic acid. The lipidic compounds as disclosed herein comprise at least one terminal radical of formula (I): *-NH-CX-(NH)n-A (I) wherein: - *- represents a single bond linking said radical of formula (I), directly or not, to to one C10 to C55 lipophilic or hydrophobic tail-group; - n is 0 or 1; - X is an oxygen or sulfur atom, and - A represents an optionally substituted 5- or 6-membered unsaturated heterocyclic radical or 5- or 6-membered heteroaromatic ring radical, both containing at least one nitrogen atom; or one of the pharmaceutically acceptable salts of said radical of formula (I); and with said compound that is in all the possible racemic, enantiomeric and diastereoisomeric isomer forms.

  该披露涉及新型脂质化合物，含有该脂质化合物的脂质纳米颗粒（LNPs），以及利用该脂质化合物或LNPs用于传递核酸。所述的脂质化合物至少包括一个式（I）的末端基团：*-NH-CX-(NH)n-A（I）其中：- *-代表连接所述式（I）的基团的单键，直接或间接地，连接到一个C10至C55的亲脂性或疏水性尾基团；- n为0或1；- X为氧或硫原子，- A代表一个可选择地取代的含有至少一个氮原子的5-或6-成员不饱和杂环基团或5-或6-成员杂芳环基团；或所述的式（I）基团的药学上可接受的盐之一；以及与所述化合物一起，以所有可能的外消旋、对映异构体和顺反异构体形式存在。
• [EN] CLEAVABLE LIPIDIC COMPOUNDS, COMPOSITIONS CONTAINING THEREOF, AND USES THEREOF<br/>[FR] COMPOSÉS LIPIDIQUES CLIVABLES, COMPOSITIONS LES CONTENANT ET UTILISATIONS ASSOCIÉES
  申请人：SANOFI PASTEUR

  公开号：WO2022013439A1

  公开（公告）日：2022-01-20

  The disclosure relates to novel lipidic compounds, method of manufacturing lipid nanoparticles (LNPs) containing thereof, lipid nanoparticles (LNPs) containing thereof, and the use of the LNPs for the delivery of nucleic acid. The lipidic compounds as disclosed herein is a cleavable lipidic compound comprising at least one terminal radical of formula (I): Y-(CHR)n-Z-(CHR')p-Q * (I) wherein: - * is the end linked, directly or not, to one C10 to C55 lipophilic or hydrophobic tail-group; - Y is a radical selected in the group consisting of methyl, methoxy, trifluoromethyl, imidazolyl, or is one hydrogen; - Z is a radical -NH-CH2-CO-O-** or a radical -CR''(NH2)-CO-O-** with ** that is the end closest to Q and R'' that is selected in the group consisting of hydrogen, methyl radical and trifluoromethyl radical; - Q is a radical -NH-CH2-CO-O-*** or a radical -CR''(NH2)-CO-O-*** with R'' selected in the group consisting of hydrogen, methyl radical and trifluoromethyl radical and *** that is the end linked, directly or not, to said lipophilic or hydrophobic tail-group; - R et R' are, independently one from the other, one hydrogen, one methyl radical or one trifluoromethyl radical; - n et p are independently one from the other 0, 1 or 2; or one of its pharmaceutically acceptable salts and with said compound being in all the possible racemic, enantiomeric and diastereoisomeric isomer forms.

  该披露涉及新型脂质化合物，制造含有脂质纳米颗粒（LNPs）的方法，含有脂质纳米颗粒（LNPs），以及将LNPs用于传递核酸。所述的脂质化合物是一种可切割的脂质化合物，包括至少一个式（I）的末端基团：Y-(CHR)n-Z-(CHR')p-Q *（I）其中：- *是末端连接的，直接或间接连接到一个C10至C55的亲脂性或疏水性尾基团；- Y是在甲基，甲氧基，三氟甲基，咪唑基中选择的基团，或是一个氢原子；- Z是一个基团-NH-CH2-CO-O-**或一个基团-CR''(NH2)-CO-O-**，其中**是最接近Q的末端，R''在氢原子，甲基基团和三氟甲基基团中选择；- Q是一个基团-NH- -CO-O-***或一个基团-CR''(NH2)-CO-O-***，其中R''在氢原子，甲基基团和三氟甲基基团中选择，***是直接或间接连接到所述亲脂性或疏水性尾基团的末端；- R和R'是彼此独立的氢原子，甲基基团或三氟甲基基团；- n和p是彼此独立的0、1或2；或其药用可接受的盐，所述化合物以所有可能的外消旋、对映异构体和顄对映异构体形式存在。