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A bioorthogonal chemical reporter of viral infection


Neef, Anne B; Pernot, Lucile; Schreier, Verena N; Scapozza, Leonardo; Luedtke, Nathan W (2015). A bioorthogonal chemical reporter of viral infection. Angewandte Chemie Internationale Edition, 54(27):7911-7914.

Abstract

Pathogen-selective labeling was achieved by using the novel gemcitabine metabolite analogue 2′-deoxy-2′,2′-difluoro-5-ethynyluridine (dF-EdU) and click chemistry. Cells infected with Herpes Simplex Virus-1 (HSV-1), but not uninfected cells, exhibit nuclear staining upon the addition of dF-EdU and a fluorescent azide. The incorporation of the dF-EdU into DNA depends on its phosphorylation by a herpes virus thymidine kinase (TK). Crystallographic analyses revealed how dF-EdU is well accommodated in the active site of HSV-1 TK, but steric clashes prevent dF-EdU from binding human TK. These results provide the first example of pathogen-enzyme-dependent incorporation and labeling of bioorthogonal functional groups in human cells.

Abstract

Pathogen-selective labeling was achieved by using the novel gemcitabine metabolite analogue 2′-deoxy-2′,2′-difluoro-5-ethynyluridine (dF-EdU) and click chemistry. Cells infected with Herpes Simplex Virus-1 (HSV-1), but not uninfected cells, exhibit nuclear staining upon the addition of dF-EdU and a fluorescent azide. The incorporation of the dF-EdU into DNA depends on its phosphorylation by a herpes virus thymidine kinase (TK). Crystallographic analyses revealed how dF-EdU is well accommodated in the active site of HSV-1 TK, but steric clashes prevent dF-EdU from binding human TK. These results provide the first example of pathogen-enzyme-dependent incorporation and labeling of bioorthogonal functional groups in human cells.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:14 May 2015
Deposited On:21 Dec 2015 13:55
Last Modified:08 Dec 2017 16:02
Publisher:Wiley-VCH Verlag
ISSN:1433-7851
Publisher DOI:https://doi.org/10.1002/anie.201500250

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