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.
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.
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2,2,5,5-四甲基吡咯烷-3-酮-1-亚磺酰基在 DNA 寡核苷酸固相制备中对脱氧核糖核苷亚磷酰胺进行 5-羟基保护。
DOI：
10.1021/ja048377i
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发表时间：
2004
影响因子：
15
通讯作者：
Beaucage,SergeL
中科院分区：
文献类型：
--
作者：
Marchan,Vicente;Cieyylak,Jacek;Livengood,Victor;Beaucage,SergeL
几种氮硫试剂已被研究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中，2,2,5,5-四甲基吡咯烷-3-一-1-亚磺酰基凭借其温和的脱保护条件，表现出近乎最佳的 5'-羟基保护性能。具体来说，在可控孔径玻璃上合成 5'-d(ATCCGTAGCCAAGGTCATGT) 时，通过在酸性盐存在下用碘处理，可以有效地完成末端 5'-亚磺酰胺基团的迭代裂解。暴露于蛇毒磷酸二酯酶和细菌碱性磷酸酶后，寡核苷酸水解为其 2'-脱氧核糖核苷，未发现任何核碱基加合物或其他修饰的形成。这些发现表明，亚磷酰胺（例如10a-d）的5'-羟基保护的2,2,5,5-四甲基吡咯烷-3-one-1-亚磺酰基可能导致寡核苷酸微阵列的产生，在核酸靶标的检测中表现出增强的特异性和灵敏度。
Several 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 mildness of its deprotection conditions. Specifically, the iterative cleavage of a terminal 5‘-sulfamidite group in the synthesis of 5‘-d(ATCCGTAGCCAAGGTCATGT) on controlled-pore glass is efficiently accomplished by treatment with iodine in the presence of an acidic salt. Hydrolysis of the oligonucleotide to its 2‘-deoxyribonucleosides upon exposure to snake venom phosphodiesterase and bacterial alkaline phosphatase did not reveal the formation of any nucleobase adducts or other modifications. These findings indicate that the 2,2,5,5-tetramethylpyrrolidin-3-one-1-sulfinyl group for 5‘-hydroxyl protection of phosphoramidites, such as10a−d, may lead to the production of oligonucleotide microarrays exhibiting enhanced specificity and sensitivity in the detection of nucleic acid targets.