Solid-Phase Synthesis of Oligonucleotide 5′-(α-P-Thio)triphosphates and 5′-(α-P-Thio)(β,γ-methylene)triphosphates

被引：5

作者：

Thillier, Yann ^{[1
]}

Sallamand, Corinne ^{[1
]}

Baraguey, Carine ^{[1
]}

Vasseur, Jean-Jacques ^{[1
]}

Debart, Francoise ^{[1
]}

机构：

[1] Univ Montpellier 2, IBMM, UMR 5247, CNRS,Univ Montpellier 1, F-34095 Montpellier 05, France

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2015年 / 2015卷 / 02期

关键词：

Solid-phase synthesis; Phosphorylation; Oligonucleotides; RNA; Triphosphates; Thiotriphosphates; NUCLEOSIDE 5'-TRIPHOSPHATES; EFFICIENT SYNTHESIS; MESSENGER-RNA; ANALOGS; PYROPHOSPHATE; TRIPHOSPHATES; DEGRADATION;

D O I：

10.1002/ejoc.201403381

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A robust solid-phase synthesis was developed to obtain original oligonucleotides (ONs) functionalized at their 5' end with modified triphosphate (TP) moieties, in which a nonbridging oxygen atom of the a phosphorus atom was replaced by a sulfur atom and the labile P-O-P linkage was changed into a methylene bridge between the beta and gamma phosphorus atoms. The efficient method is based on solid-supported ON assembly followed by 5'-H-phosphonylation, oxidation to the thiophosphate subsequently activated as a phosphoan-hydride with diphenyl phosphoryl chloride, then nucleophilic substitution with the alkylammonium salt of pyrophosphate or its beta,gamma-methylene analogue. After deprotection and release from the solid support under basic conditions, 5'-(alpha-P-thio)TP and 5'-(alpha-P-thio)(beta,gamma-methylene) TP oligonucleotides were obtained in satisfactory yields, and they were isolated with high purity. These hydrolysis-resistant 5'-TP ONs will be useful in biological research to elucidate the mechanism of enzymes involved in mRNA processing and maturation.

引用

页码：302 / 308

页数：7

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