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Issue 4, 2016

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

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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.

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

Supplementary files

Article information

01 Jan 2016
28 Jan 2016
First published
28 Jan 2016

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2016,7, 2516-2523
Article type
Edge Article

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

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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