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

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 remains a challenge in developing efficient catalysts in biochemis...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2015-10, Vol.6 (10), p.5578-5585
Main Authors: Li, Yinghao, Cheng, Mingpan, Hao, Jingya, Wang, Changhao, Jia, Guoqing, Li, Can
Format: Article
Language:English
Subjects:
Biochemistry
Catalysis
Catalysts
Chemistry
Deoxyribonucleic acid
Human
Human performance
Inspiration
Regulators
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Summary: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 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 (CuL ) 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.
ISSN:2041-6520
2041-6539
DOI:10.1039/c5sc01381j