Synthesis of antisense oligonucleotides using environmentally friendly and safe deprotection procedures
Synthesis of antisense oligonucleotides using environmentally friendly and safe deprotection procedures
复制标题
DOI：
10.1039/a907685i
复制
发表时间：
1999-12-01
期刊：
影响因子：
9.8
通讯作者：
Ravikumar, VT
中科院分区：
文献类型：
--
作者：
Krotz, AH;Carty, RL;Ravikumar, VT
结果表明，混合序列硫代磷酸寡脱氧核糖核苷酸可以在不使用二氯甲烷等氯化溶剂的情况下以高达 80 mmol 的规模合成，同时保持产品的高产率和纯度。在固相支持物上合成过程中，二氯乙酸的甲苯溶液可清洁有效地去除生长寡核苷酸链 5' 末端的 4,4'-二甲氧基三苯甲基。在室温和大气压下进行氢氧化铵处理可提供脱保护的寡核苷酸，从而降低加压反应玻璃容器造成的风险。为了确保聚合物珠（Primer HL 30）和寡核苷酸溶液的轻松分离，对反应混合物进行最小程度的搅拌。
It is demonstrated that mixed-sequence phosphorothioate oligodeoxyribonucleotides can be synthesized on scales up to 80 mmol without using chlorinated solvents like dichloromethane, while preserving both high yield and purity of the product. A solution of dichloroacetic acid in toluene cleanly and efficiently removes 4,4'-dimethoxytrityl groups from the 5'-terminus of the growing oligonucleotide chain during synthesis on solid support. Ammonium hydroxide treatment at room temperature at atmospheric pressure furnishes deprotected oligonucleotides reducing the risk that pressurized reaction glass vessels pose. To ensure facile separation of polymer beads (Primer HL 30) and oligonucleotide solution, minimum agitation of the reaction mixture is applied.