Journal
CHEMICAL SCIENCE
Volume 7, Issue 4, Pages 2516-2523Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6sc00001k
Keywords
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Funding
- Hong Kong Baptist University [FRG2/14-15/004]
- Health and Medical Research Fund [HMRF/14130522]
- Research Grants Council [HKBU/201811, HKBU/204612, HKBU/201913]
- French Agence Nationale de la Recherche/Research Grants Council Joint Research Scheme [A-HKBU201/12, ANR-12-IS07-0001]
- National Natural Science Foundation of China [21575121]
- Guangdong Province Natural Science Foundation [2015A030313816]
- Hong Kong Baptist University Century Club Sponsorship Scheme
- Interdisciplinary Research Matching Scheme [RC-IRMS/14-15/06]
- Science and Technology Development Fund, Macao SAR [098/2014/A2]
- University of Macau [MYRG091(Y3-L2)-ICMS12-LCH, MYRG2015-00137-ICMS-QRCM, MRG023/LCH/2013/ICMS, MRG044/LCH/2015/ICMS]
- Conseil regional d'Aquitaine, France
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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.
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