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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 vice versa remains a challenge in developing efficient catalysts i...

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Detalles Bibliográficos
Autores principales: Li, Yinghao, Cheng, Mingpan, Hao, Jingya, Wang, Changhao, Jia, Guoqing, Li, Can
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949855/
https://www.ncbi.nlm.nih.gov/pubmed/29861895
http://dx.doi.org/10.1039/c5sc01381j
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author Li, Yinghao
Cheng, Mingpan
Hao, Jingya
Wang, Changhao
Jia, Guoqing
Li, Can
author_facet Li, Yinghao
Cheng, Mingpan
Hao, Jingya
Wang, Changhao
Jia, Guoqing
Li, Can
author_sort Li, Yinghao
collection PubMed
description 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.
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spelling pubmed-59498552018-06-01 Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme Li, Yinghao Cheng, Mingpan Hao, Jingya Wang, Changhao Jia, Guoqing Li, Can Chem Sci Chemistry 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. Royal Society of Chemistry 2015-10-01 2015-06-24 /pmc/articles/PMC5949855/ /pubmed/29861895 http://dx.doi.org/10.1039/c5sc01381j Text en This journal is © The Royal Society of Chemistry 2015 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Li, Yinghao
Cheng, Mingpan
Hao, Jingya
Wang, Changhao
Jia, Guoqing
Li, Can
Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
title Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
title_full Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
title_fullStr Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
title_full_unstemmed Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
title_short Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
title_sort terpyridine–cu(ii) targeting human telomeric dna to produce highly stereospecific g-quadruplex dna metalloenzyme
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949855/
https://www.ncbi.nlm.nih.gov/pubmed/29861895
http://dx.doi.org/10.1039/c5sc01381j
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