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Charge-driven tripod somersault on DNA for ratiometric fluorescence imaging of small molecules in the nucleus

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Abstract

Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named “charge-driven tripod somersault on DNA”, for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO32−/HSO3, a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe–DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes.

Graphical abstract: Charge-driven tripod somersault on DNA for ratiometric fluorescence imaging of small molecules in the nucleus

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Publication details

The article was received on 22 Jul 2019, accepted on 02 Sep 2019 and first published on 06 Sep 2019


Article type: Edge Article
DOI: 10.1039/C9SC03594J
Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Charge-driven tripod somersault on DNA for ratiometric fluorescence imaging of small molecules in the nucleus

    K. Wang, Q. Cao, L. Liu, Z. Zhao, W. Liu, D. Zhou, C. Tan, W. Xia, L. Ji and Z. Mao, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C9SC03594J

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