Conjugating a groove-binding motif to an Ir(iii) complex for the enhancement of G-quadruplex probe behavior. Issue 4 (5th February 2016)

• Record Type: Journal Article
• Authors: Wang, Modi; Mao, Zhifeng; Kang, Tian-Shu; Wong, Chun-Yuen; Mergny, Jean-Louis; Leung, Chung-Hang; Ma, Dik-Lung
• Is Part Of: Chemical science. Volume 7:Issue 4(2016:Apr.)
• Page Start: 2516
• Page End: 2523
• Publication Date: 2016-02-05
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6sc00001k
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : G-quadruplex groove binder benzo[ d, e ]isoquinoline was linked to a Ir(iii ) complex to generate a highly selective DNA probe. 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 probe1 that retains the favorable photophysical properties of the parent complex. The linked complex1 showed advantages of both parent complex2 and groove binder3 . Similar to3, the conjugated complex1 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 complex2 . The molecular modelling revealed a groove-binding mode between complex1 and G-quadruplex. Meanwhile1 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 employed1 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.