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  • br Experimental section br Results and discussion br Conclus

    2021-09-14


    Experimental section
    Results and discussion
    Conclusions To summarize, the act of conjugating a ASC ligands to a Ru(II) polypyridyl subunits resulted in a class of excellent DNA binders. A comparison of the DNA binding abilities of the free ASC ligand and the complexes, has revealed that the octahedral Ru(II) center played a crucial role in yielding good G-quadruplex and duplex DNA binders. Among three new complexes, complex 3 exhibited the strongest G-quadruplex and duplex DNA stabilization ability. Complex 3 was determined to be the most promising candidate for further in vitro studies and to be a potent anticancer drug. Though these complexes showed lack of selectivity for G-quadruplex over duplex DNA, the present work provides the basis for the rational development of ASC derivatives as promising telomerase inhibitors and potential anticancer drugs.
    Abbreviations
    Acknowledgements This work was supported by the National Natural Science Foundation of China (No. 21671150, 21877084, 81871730 and 21472139), Science and Technology Commission of Shanghai Municipality (No. 14DZ2261100) and the Fundamental Research Funds for the Central Universities.
    Introduction Two-dimensional materials, such as graphene oxide, molybdenum disulfide, boron nitride, black phosphene, etc., are a new type of material with atomic thickness. Due to its unique electronic, optical and mechanical properties, it has become the most promising material in the field of technology application and basic science [[1], [2], [3], [4]]. Among them, molybdenum disulfide (MoS2), have been attracting more phospholipase c inhibitor attention in the last few years because of its excellent nanoelectronics [5], optoelectronics [6], and phospholipase c inhibitor harvesting properties [7]. Very recently, MoS2 nanosheets were demonstrated to be able to spontaneously adsorb single-strand DNA by the van der Waals force between nucleobases and the basal plane of MoS2 nanosheets, acting as an efficient dye quencher for a two-step assay of DNA, small molecules, protein, and metal ion etc. For example, Huang et al. developed a novel MoS2-based fluorescent nanoprobe for detecting DNA [8]. Zhu et al. reported a simple and homogeneous assay format for ATP by using single-layer MoS2-based fluorogenic nanoprobes [9]. Kenry et al. built a fluorescence resonant energy transfer-based aptasensing platform using single-layer MoS2 nanosheets for the detection of plasmodium lactate dehydrogenase protein [10]. Mao et al. also prepared single-layer MoS2 nanosheets biosensor for detection of Ag+ [11]. These assays have low background signals. However, dye-labeled DNA probes is necessary for the construction of fluorescence sensors and it is high-cost and time-consuming in design. Therefore, designing a label-free, low-background MoS2-based sensor for high-sensitive detection of biomolecule is desired. MicroRNAs (miRNAs) are small noncoding RNA molecules with approximately 19–25 nucleotides, which play important regulatory roles in cell division, differentiation, and apoptosis [12,13]. However, it is still a significant challenge to sensitively and selectively detecting the miRNAs due to their short length, low abundance, and sequence homology among family members [14]. In order to detect low concentrations of miRNA, many amplification strategies for miRNA detection have been developed, including polymerase chain reaction [15], ligase chain reaction [16], rolling circle amplification [17], and Exonuclease III-Aided Target Recycling [18]. These strategies are highly enzyme-dependent, which require harsh reaction environment such as pH, temperature, and buffer component. Compared with these methods, hybridization chain reaction (HCR) is an enzyme-free emerging techniques for signal amplification and detection of targets amplification with the advantages of high sensitivity and low-cost [19,20]. However, the current reported HCR-based fluorescence methods for miRNA detection require modification of fluorophores and quenchers [21,22]. This complicated chemical modification leads to a significant increase in the labor and cost. Therefore, by exploiting the capability of reducing background signal of MoS2 combine with high sensitivity and low-cost of HCR signal amplification, we seek to construct a label-free and enzyme-free fluorescence strategy for miRNA detection with high selectivity and high sensitivity. As far as we know, there is no report about MoS2-loaded G-quadruplex molecular beacon probes for miRNAs detection through HCR signal amplification.