Ethynyl Side Chain Hydration during Synthesis and Workup of "Clickable" Oligonucleotides: Bypassing Acetyl Group Formation by Triisopropylsilyl Protection
Ethynyl Side Chain Hydration during Synthesis and Workup of "Clickable" Oligonucleotides: Bypassing Acetyl Group Formation by Triisopropylsilyl Protection
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DOI：
10.1021/jo401780u
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发表时间：
2013-11-15
影响因子：
3.6
通讯作者：
Seela, Frank
中科院分区：
文献类型：
--
作者：
Ingale, Sachin A.;Mei, Hui;Seela, Frank
嘧啶 5 位（(eth)dC 和 (eth)dU）或 7-脱氮鸟嘌呤（(eth)c(7)G(d)）7 位具有乙炔基残基的可点击寡核苷酸在固相寡核苷酸合成和后处理条件下会发生水合。通过寡核苷酸的 MALDI-TOF 质谱和酶促磷酸二酯水解后修饰核苷的检测，将副产物鉴定为乙酰基衍生物。还研究了酸性和碱性条件下乙炔基->乙酰基的乙炔基核苷转化。可以证明侧链转换取决于核碱基结构。引入三异丙基甲硅烷基残基以保护乙炔基残基免于水合。在所有情况下，在脱甲硅烷基化后均分离出纯的、不含乙酰基的寡核苷酸。
Clickable oligonucleotides with ethynyl residues in the 5-position of pyrimidines ((eth)dC and (eth)dU) or the 7-position of 7-deazaguanine ((eth)c(7)G(d)) are hydrated during solid-phase oligonucleotide synthesis and workup conditions. The side products were identified as acetyl derivatives by MALDI-TOF mass spectra of oligonucleotides and by detection of modified nucleosides after enzymatic phosphodiester hydrolysis. Ethynyl -> acetyl group conversion was also studied on ethynylated nucleosides under acidic and basic conditions. It could be shown that side chain conversion depends on the nucleobase structure. Triisopropylsilyl residues were introduced to protect ethynyl residues from hydration. Pure, acetyl group free oligonucleotides were isolated after desilylation in all cases.