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Issue 4, 2016
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Conjugating a groove-binding motif to an Ir(III) complex for the enhancement of G-quadruplex probe behavior

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Abstract

In this study, the reported G-quadruplex groove binder benzo[d,e]isoquinoline was linked to a cyclometallated Ir(III) complex to generate a highly selective DNA probe 1 that retains the favorable photophysical properties of the parent complex. The linked complex 1 showed advantages of both parent complex 2 and groove binder 3. Similar to 3, the conjugated complex 1 exhibits a superior affinity and selectivity for G-quadruplex DNA over other conformations of DNA or proteins, with the fold enhancement ratio obviously improved compared with parent complex 2. The molecular modelling revealed a groove-binding mode between complex 1 and G-quadruplex. Meanwhile 1 also possesses the prominent advantages of transition metal complex probes such as a large Stokes shift and long lifetime phosphorescence, which could be recognized in strong fluorescence media through time-resolved emission spectroscopy (TRES). We then employed 1 to develop a detection assay for AGR2, a potential cancer biomarker, as a “proof-of-principle” demonstration of the application of a linked complex for DNA-based detection in diluted fetal bovine serum. We anticipate that this conjugation method may be further employed in the development of DNA probes and have applications in label-free DNA-based diagnostic platforms.

Graphical abstract: Conjugating a groove-binding motif to an Ir(iii) complex for the enhancement of G-quadruplex probe behavior

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Publication details

The article was received on 01 jan. 2016, accepted on 28 jan. 2016 and first published on 28 jan. 2016


Article type: Edge Article
DOI: 10.1039/C6SC00001K
Citation: Chem. Sci., 2016,7, 2516-2523
  • Open access: Creative Commons BY license
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    Conjugating a groove-binding motif to an Ir(III) complex for the enhancement of G-quadruplex probe behavior

    M. Wang, Z. Mao, T. Kang, C. Wong, J. Mergny, C. Leung and D. Ma, Chem. Sci., 2016, 7, 2516
    DOI: 10.1039/C6SC00001K

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