Sensitive Oligodeoxynucleotide Synthesis Using Dim and Dmoc as Protecting Groups.
Sensitive Oligodeoxynucleotide Synthesis Using Dim and Dmoc as Protecting Groups.
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DOI：
10.1021/acs.joc.9b01527
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发表时间：
2019-09
期刊：
影响因子：
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通讯作者：
Shahien Shahsavari;Dhananjani N A M Eriyagama;Jinsen Chen;Bhaskar Halami;Yipeng Yin;Komal Chillar;Shiyue Fang
中科院分区：
文献类型：
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作者：
Shahien Shahsavari;Dhananjani N A M Eriyagama;Jinsen Chen;Bhaskar Halami;Yipeng Yin;Komal Chillar;Shiyue Fang
在传统的寡脱氧核苷酸（ODN）合成中，磷酸基被2-氰乙基保护，氨基被酰基保护。在ODN合成结束时，通过强碱和亲核试剂实现脱保护。因此，传统技术不适合合成含有敏感官能团的odn。为了解决这个问题，我们报道了在固相ODN合成中使用基于1,3-二硫代-2-甲基功能的Dim和Dmoc基团来保护磷酸盐和胺。使用新的Dim-Dmoc保护剂，在温和的氧化条件下实现脱保护，不使用任何强碱和亲核试剂。因此，新工艺适用于含敏感功能的odn的合成。为了证明其可行性，我们合成了7个20聚odn，其中4个含有敏感的酯和烷基氯基团，用RP - HPLC纯化，用MALDI-TOF MS和酶切论文对其进行了表征。得到了高纯度的odn。
In traditional oligodeoxynucleotide (ODN) synthesis, phosphate groups are protected with 2-cyanoethyl group, and amino groups are protected with acyl groups. At the end of ODN synthesis, deprotection is achieved with strong bases and nucleophiles. Therefore, traditional technologies are not suitable for the synthesis of ODNs containing sensitive functionalities. To address the problem, we report the use of Dim and Dmoc groups, which are based on the 1,3-dithian-2-yl-methyl function, for phosphate and amine protection for solid phase ODN synthesis. Using the new Dim-Dmoc protection, deprotection was achieved under mild oxidative conditions without using any strong bases and nucleophiles. As a result, the new technology is suitable for the synthesis of ODNs containing sensitive functions. To demonstrate feasibility, seven 20-mer ODNs including four that contain the sensitive ester and alkyl chloride groups were synthesized, purified with RP HPLC and characterized with MALDI-TOF MS and enzyme digestion essays. High purity ODNs were obtained.