阳离子亚甲基蓝主链聚合物的合成及 DNA 切割活性,ACS Applied Bio Materials

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阳离子亚甲基蓝主链聚合物的合成及 DNA 切割活性
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2023-05-19 , DOI: 10.1021/acsabm.3c00170
Xuetong Cai ₁ , Xiaoran Zhang ₁ , Yajie Zhang ₂ , Fude Feng ₁

Affiliation

DNA 切割方法在基因编辑、疾病治疗和生物传感器设计方面具有广泛的生物应用。传统的DNA切割方法主要是通过小分子或过渡金属配合物介导的氧化或水解。然而，使用有机聚合物通过人工核酸酶切割DNA的报道却很少。亚甲蓝因其优异的单线态氧产率、氧化还原性能和良好的DNA亲和力而在生物医学和生物传感领域得到广泛研究。亚甲蓝主要依靠光和氧进行DNA切割，切割速度慢。在这里，我们合成了阳离子亚甲基蓝主链聚合物（MBP），它可以在没有光和外源试剂的情况下有效结合DNA并通过自由基机制诱导DNA裂解，表现出高效的核酸酶活性。此外，不同结构的MBP对DNA切割均表现出选择性，柔性结构的切割效率显着高于刚性结构。DNA裂解机制的研究表明，MBPs的裂解机制不是通过常见的ROS介导的氧化裂解途径，而是通过MBP的自由基^•诱导DNA 裂解。同时，MBP可以模拟拓扑异构酶I（Topo I）介导的超螺旋DNA拓扑重排。该工作为MBPs在人工核酸酶领域的应用铺平了道路。

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Synthesis and DNA Cleavage Activity of Cationic Methylene-Blue-Backboned Polymers

Methods of DNA cleavage have broad bioapplications in gene editing, disease treatment, and biosensor design. The traditional method for DNA cleavage is mainly through oxidation or hydrolysis mediated by small molecules or transition metal complexes. However, DNA cleavage by artificial nucleases using organic polymers has been rarely reported. Methylene blue has been extensively studied in the fields of biomedicine and biosensing due to its excellent singlet oxygen yield, redox properties, and good DNA affinity. Methylene blue mainly relies on light and oxygen for DNA cleavage, and the cutting rate is slow. Here, we synthesize cationic methylene-blue-backboned polymers (MBPs) that can bind DNA efficiently and induce DNA cleavage through free radical mechanisms in the absence of light and exogenous reagents, showing high-efficiency nuclease activity. In addition, MBPs with different structures showed selectivity for DNA cleavage, and the cleavage efficiency of the flexible structure was significantly higher than that of the rigid structure. Studies on the DNA cleavage mechanism have shown that the cleavage mechanism of MBPs is not through the common ROS-mediated oxidative cleavage pathway, but through the radical of MBP^• inducing DNA cleavage. Meanwhile, MBPs can simulate topoisomerase I (Topo I)-mediated topological rearrangement of superhelical DNA. This work paved a way for the application of MBPs in the field of artificial nucleases.

更新日期：2023-05-19

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