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Issue 10, 2015
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Terpyridine–Cu(II) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme

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Abstract

The cofactors commonly involved in natural enzymes have provided the inspiration for numerous advances in the creation of artificial metalloenzymes. Nevertheless, to design an appropriate cofactor for a given biomolecular scaffold or vice versa remains a challenge in developing efficient catalysts in biochemistry. Herein, we extend the idea of G-quadruplex-targeting anticancer drug design to construct a G-quadruplex DNA metalloenzyme. We found that a series of terpyridine–Cu(II) complexes (CuLn) can serve as excellent cofactors to dock with human telemetric G-quadruplex DNA. The resulting G-quadruplex DNA metalloenzyme utilising CuL1 catalyzes an enantioselective Diels–Alder reaction with enantioselectivity of >99% enantiomeric excess and about 73-fold rate acceleration compared to CuL1 alone. The terpyridine–Cu(II) complex cofactors demonstrate dual functions, both as an active site to perform catalysis and as a structural regulator to promote the folding of human telemetric G-quadruplex DNA towards excellent catalysts.

Graphical abstract: Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme

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Publication details

The article was received on 16 Apr 2015, accepted on 23 Jun 2015 and first published on 24 Jun 2015


Article type: Edge Article
DOI: 10.1039/C5SC01381J
Citation: Chem. Sci., 2015,6, 5578-5585
  • Open access: Creative Commons BY license
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    Terpyridine–Cu(II) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme

    Y. Li, M. Cheng, J. Hao, C. Wang, G. Jia and C. Li, Chem. Sci., 2015, 6, 5578
    DOI: 10.1039/C5SC01381J

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