Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)–DNA Conjugates,Journal of the American Chemical Society

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Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)–DNA Conjugates
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2017-07-26 00:00:00 , DOI: 10.1021/jacs.7b05064
Fei Jia ₁ , Xueguang Lu ₁ , Dali Wang ₁ , Xueyan Cao ₁ , Xuyu Tan ₁ , Hao Lu ₁ , Ke Zhang ₁

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PEGylation of an oligonucleotide using a brush polymer can improve its biopharmaceutical characteristics, including enzymatic stability and biodistribution. Herein, we quantitatively explore the nuclease accessibility of the nucleic acid as a function of “depth” toward the backbone of the brush polymer. It is found that protein accessibility decreases as the nucleotide is located closer to the backbone. Thus, by moving the conjugation point from the terminus of the nucleic acid strand to an internal position, much smaller brushes can be used to achieve the same level of steric shielding. This finding also makes it possible to assess antisense gene regulation efficiency of these brush–DNA conjugates as a function of their nuclease stability.

中文翻译：

深度构图的刷状结构的聚乙二醇-DNA结合物的核酸酶稳定性和基因沉默功效。

使用刷状聚合物对寡核苷酸进行聚乙二醇化可以改善其生物药物特性，包括酶稳定性和生物分布。在本文中，我们定量地探究了核酸的核酸酶可及性，它是朝向刷子聚合物主链的“深度”的函数。已经发现，蛋白质的可及性随着核苷酸靠近主链而降低。因此，通过将结合点从核酸链的末端移动到内部位置，可以使用小得多的刷子来实现相同水平的空间屏蔽。这一发现也使评估这些brush-DNA结合物的反义基因调控效率与它们的核酸酶稳定性之间的关系成为可能。

更新日期：2017-07-28

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