Systematic optimization and modification of a DNA aptamer with 2'-O-methyl RNA analogues.

Systematic optimization and modification of a DNA aptamer with 2'-O-methyl RNA analogues.
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DOI:
10.1002/slct.201700359
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发表时间:
2017-03-01
期刊:
影响因子:
2.1
通讯作者:
Mallikaratchy P
Mallikaratchy P
中科院分区:
化学4区
文献类型:
--
作者:
Maio G;Enweronye O;Zumrut HE;Batool S;Van N;Mallikaratchy P

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核酸适体(NAAs)是一种短的合成DNA或RNA分子,可以折叠成独特的三维结构,能够特异性识别靶标。虽然NAAs在包括传感、治疗和诊断在内的各种应用中显示出前所未有的前景,但一个主要的限制是缺乏对无所不在的核酸酶的稳定性。因此,我们在此报告了一种系统截断并将2 ' - o -甲基碱基掺入DNA适体的方法,这在不影响亲和力的情况下提高了稳定性。其中一种新设计的类似物在24小时内是稳定的,这表明2 ' - o -甲基RNA是DNA适体的一种有吸引力的修饰,特别是在治疗应用的时候。系统截断并将2 ' - o -甲基碱基掺入DNA适体,增加了稳定性而不影响亲和力。
Nucleic acid aptamers (NAAs) are short synthetic DNA or RNA molecules that specifically fold into distinct three-dimensional structures able to specifically recognize a target. While NAAs show unprecedented promise in a variety of applications, including sensing, therapeutics and diagnostics, one major limitation involves the lack of stability towards omnipresent nucleases. Therefore, we herein report a systematic truncation and incorporation of 2′-O-methyl bases to a DNA aptamer, which results in increased stability without affecting affinity. One of the newly designed analogues is stable up to 24 hours, demonstrating that 2′-O-methyl RNA is an attractive modification to DNA aptamers, especially when therapeutic applications are intended. The systematic truncation and incorporation of 2′-O-methyl bases to a DNA aptamer resulted in increased stability without affecting affinity.
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