三磷酸核苷及其类似物的快速合成。

Q4 Chemistry
Alexander Ripp, Jyoti Singh, Henning J Jessen
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引用次数: 0

摘要

三磷酸核苷(NTPs)是参与几乎所有生物过程的基本生物分子,因此对它们的研究对于理解细胞生物学至关重要。在这里,我们描述了一种适合于获得天然和高度修饰的ntp的化学合成,例如,它可以用作探测生物过程的替代品。该方法包括制备一种试剂,该试剂能够容易地引入和修饰三种磷酸盐单元:从焦磷酸盐(PV)衍生的环焦磷酸基P-amidite (c-PyPA)和活性磷酰胺(PIII)。通过使用焦磷酸盐的不可水解类似物,可以很容易地对试剂进行修饰,得到一系列含有CH2, CF2, CCl2和nh3的不可水解类似物,如果储存得当,这些类似物在溶液中可以稳定数周。它们与核苷反应生成脱氧环三磷酸酯,然后氧化为环三磷酸酯(环- tp)。不同氧化剂的使用为P-α的修饰提供了机会。此外,P-γ的末端修饰可以通过环tp酯与各种亲核试剂的线性化来引入。©2020作者。基本方案1:环焦磷酰p -酰胺(c-PyPA)及其衍生物(c-PyNH PA、c-PyCH2 PA、c-PyCCl2 PA、c-PyCF2 PA)的合成基本方案2:3′-叠氮胸苷5′-γ- p -丙基氨基三磷酸及其类似物的合成基本方案3:2′-脱氧胸苷5′-γ- p -丙基氨基三磷酸的合成(15)基本方案4:5′-γ- p -氨基三磷酸腺苷的合成(19)和5′-γ- p -丙基氨基三磷酸腺苷的合成(20)基本方案5:d4t5′-γ-丙基酰胺β,γ-(二氟乙烯)三磷酸的合成支持方案:二氯二异丙基磷酰胺的合成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Rapid Synthesis of Nucleoside Triphosphates and Analogues.

Nucleoside triphosphates (NTPs) are essential biomolecules involved in almost all biological processes, and their study is therefore critical to understanding cellular biology. Here, we describe a chemical synthesis suitable for obtaining both natural and highly modified NTPs, which can, for example, be used as surrogates to probe biological processes. The approach includes the preparation of a reagent that enables the facile introduction and modification of three phosphate units: cyclic pyrophosphoryl P-amidite (c-PyPA), derived from pyrophosphate (PV ) and a reactive phosphoramidite (PIII ). By using non-hydrolyzable analogues of pyrophosphate, the reagent can be readily modified to obtain a family of non-hydrolyzable analogues containing CH2 , CF2 , CCl2 , and NH that are stable in solution for several weeks if stored appropriately. They enable the synthesis of NTPs by reaction with nucleosides to give deoxycyclotriphosphate esters that are then oxidized to cyclotriphosphate (cyclo-TP) esters. The use of different oxidizing agents provides an opportunity for modification at P-α. Furthermore, terminal modifications at P-γ can be introduced by linearization of the cyclo-TP ester with various nucleophiles. © 2020 The Authors. Basic Protocol 1: Synthesis of cyclic pyrophosphoryl P-amidite (c-PyPA) and derivatives (c-PyNH PA, c-PyCH2 PA, c-PyCCl2 PA, c-PyCF2 PA) Basic Protocol 2: Synthesis of 3'-azidothymidine 5'-γ-P-propargylamido triphosphates and analogues Basic Protocol 3: Synthesis of 2'-deoxythymidine 5'-γ-P-propargylamido triphosphate (15) Basic Protocol 4: Synthesis of adenosine 5'-γ-P-amido triphosphate (19) and adenosine 5'-γ-P-propargylamido triphosphate (20) Basic Protocol 5: Synthesis of d4T 5'-γ-propargylamido β,γ-(difluoromethylene)triphosphate Support Protocol: Synthesis of diisopropylphosphoramidous dichloride.

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来源期刊
Current Protocols in Nucleic Acid Chemistry
Current Protocols in Nucleic Acid Chemistry Chemistry-Organic Chemistry
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期刊介绍: Published in association with International Society for Nucleosides, Nucleotides & Nucleic Acids (IS3NA) , Current Protocols in Nucleic Acid Chemistry is equally valuable for biotech, pharmaceutical, and academic labs. It is the resource for designing and running successful research projects in the rapidly growing and changing field of nucleic acid, nucleotide, and nucleoside research.
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