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

• 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
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c5sc01381j

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.