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

Modi Wang, Zhifeng Mao, Tian Shu Kang, Chun Yuen Wong, Jean Louis Mergny*, Chung Hang Leung, Edmond Dik Lung MA

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2516-2523
Number of pages8
JournalChemical Science
Volume7
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016

Scopus Subject Areas

  • Chemistry(all)

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