2,2,5,5-Tetramethylpyrrolidin-3-one-1-sulfinyl Group for 5‘-Hydroxyl Protection of Deoxyribonucleoside Phosphoramidites in the Solid-Phase Preparation of DNA Oligonucleotides
作者:Vicente Marchán、Jacek Cieślak、Victor Livengood、Serge L. Beaucage
DOI:10.1021/ja048377i
日期:2004.8.1
nitrogen-sulfur reagents have been investigated as potential 5'-hydroxyl protecting groups for deoxyribonucleoside phosphoramidites to improve the synthesis of oligonucleotides on glass microarrays. Out of the nitrogen-sulfur-based protecting groups so far investigated, the 2,2,5,5-tetramethylpyrrolidin-3-one-1-sulfinyl group exhibited near optimal properties for 5'-hydroxyl protection by virtue of the
已经研究了几种氮硫试剂作为脱氧核糖核苷亚磷酰胺的潜在 5'-羟基保护基团,以改善玻璃微阵列上寡核苷酸的合成。在迄今为止研究的氮硫基保护基团中,2,2,5,5-四甲基吡咯烷-3-one-1-亚磺酰基由于其温和性而表现出近乎最佳的 5'-羟基保护性质。脱保护条件。具体而言,在控制孔玻璃上合成 5'-d(ATCCGTAGCCAAGGTCATGT) 时,末端 5'-亚磺酰胺基团的迭代裂解是通过在酸性盐的存在下用碘处理来有效完成的。寡核苷酸水解为其 2' -脱氧核糖核苷暴露于蛇毒磷酸二酯酶和细菌碱性磷酸酶后未显示任何核碱基加合物或其他修饰的形成。这些发现表明,用于亚磷酰胺 5'-羟基保护的 2,2,5,5-四甲基吡咯烷-3-one-1-亚磺酰基,如 10a-d,可能导致寡核苷酸微阵列的产生,其表现出增强的特异性和检测核酸靶标的灵敏度。