AMB保护基团在甲基膦酸酯DNA类似物固相合成中的应用。
The application of the AMB protective group in the solid-phase synthesis of methylphosphonate DNA analogues.
作者信息
Kuijpers W H, Kuyl-Yeheskiely E, van Boom J H, van Boeckel C A
机构信息
Organon International BV, Leiden, The Netherlands.
出版信息
Nucleic Acids Res. 1993 Jul 25;21(15):3493-500. doi: 10.1093/nar/21.15.3493.
Abstract
Partially methylphosphonate-modified oligodeoxynucleotides were synthesized on solid-phase by employing the easily removable 2-(acetoxymethyl)benzoyl (AMB) group as base-protecting group. Although a rapid AMB deprotection can be accomplished in methanolic potassium carbonate, the lability of the methylphosphonate linkage towards potassium carbonate/methanol excludes the use of this deprotection reagent. Thus, saturated ammonia solution in methanol was investigated as an alternative reagent for AMB removal. It is demonstrated that the combination of the AMB protective group and ammonia/methanol as deprotection reagent significantly improves the synthesis of methylphosphonate-modified DNA fragments. A mild overnight treatment at room temperature is sufficient for complete removal of the AMB group, whereas deprotection of conventionally protected oligonucleotides requires much longer exposure to basic conditions at elevated temperatures.
摘要
通过使用易于去除的2-(乙酰氧基甲基)苯甲酰基(AMB)基团作为碱基保护基团，在固相上合成了部分甲基膦酸酯修饰的寡脱氧核苷酸。尽管在碳酸钾甲醇溶液中可以快速实现AMB脱保护，但甲基膦酸酯键对碳酸钾/甲醇的不稳定性排除了使用这种脱保护试剂的可能性。因此，研究了甲醇中的饱和氨溶液作为去除AMB的替代试剂。结果表明，AMB保护基团与氨/甲醇作为脱保护试剂的组合显著改善了甲基膦酸酯修饰的DNA片段的合成。在室温下温和过夜处理足以完全去除AMB基团，而传统保护的寡核苷酸的脱保护需要在高温下长时间暴露于碱性条件。
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