Zhu Jinbo, Yan Zhiqiang, Bošković Filip, Haynes Cally J E, Kieffer Marion, Greenfield Jake L, Wang Jin, Nitschke Jonathan R, Keyser Ulrich F
Cavendish Laboratory, University of Cambridge JJ Thompson Avenue Cambridge CB3 0HE UK
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun Jilin 130022 P. R. China.
Chem Sci. 2021 Oct 7;12(43):14564-14569. doi: 10.1039/d1sc04430c. eCollection 2021 Nov 10.
Since the discovery of the G-quadruplex (G4) structure in telomeres in 1980s, studies have established the role it plays in various biological processes. Here we report binding between DNA G4 and a self-assembled tetrahedral metal-organic cage and consequent formation of aggregates, whereby the cage protects the DNA G4 from cleavage by S1 nuclease. We monitor DNA-cage interaction using fluorescence spectroscopy, firstly by quenching of a fluorescent label appended to the 5' end of G4. Secondly, we detect the decrease in fluorescence of the G4-selective dyes thioflavin-T and Zn-PPIX bound to various DNA G4 sequences following the addition of cage . Our results demonstrate that interacts with a wide range of G4s. Moreover, gel electrophoresis, circular dichroism and dynamic light scattering measurements establish the binding of to G4 and indicate the formation of aggregate structures. Finally, we find that DNA G4 contained in an aggregate of cage is protected from cleavage by S1 nuclease.
自20世纪80年代在端粒中发现G-四链体(G4)结构以来,研究已确定了其在各种生物过程中所起的作用。在此,我们报告了DNA G4与一种自组装四面体金属有机笼之间的结合以及由此产生的聚集体形成,其中该笼可保护DNA G4不被S1核酸酶切割。我们使用荧光光谱法监测DNA-笼相互作用,首先是通过淬灭连接到G4 5'端的荧光标记。其次,我们检测在加入笼后与各种DNA G4序列结合的G4选择性染料硫黄素-T和锌原卟啉IX的荧光降低情况。我们的结果表明,[此处原文可能缺失关键信息,未明确具体是什么与多种G4相互作用]与多种G4相互作用。此外,凝胶电泳、圆二色性和动态光散射测量确定了[此处原文可能缺失关键信息,未明确具体是什么与G4的结合]与G4的结合,并表明形成了聚集体结构。最后,我们发现包含在笼[此处原文可能缺失关键信息,未明确具体是什么笼]聚集体中的DNA G4受到保护,不被S1核酸酶切割。