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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2015
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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. |
format | Online Article Text |
id | pubmed-5949855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
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
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title_full | Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
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title_fullStr | Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
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title_full_unstemmed | Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
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title_short | Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme
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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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