A Bioorthogonal Chemical Reporter of Viral Infection.
| Autor: | Neef AB; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland) http://www.bioorganic-chemistry.com., Pernot L; Pharmaceutical Biochemistry, University of Geneva (Switzerland)., Schreier VN; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland) http://www.bioorganic-chemistry.com., Scapozza L; Pharmaceutical Biochemistry, University of Geneva (Switzerland)., Luedtke NW; Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland) http://www.bioorganic-chemistry.com. |
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| Jazyk: | angličtina |
| Zdroj: | Angewandte Chemie (Weinheim an der Bergstrasse, Germany) [Angew Chem Weinheim Bergstr Ger] 2015 Jun 26; Vol. 127 (27), pp. 8022-8025. Date of Electronic Publication: 2015 May 14. |
| DOI: | 10.1002/ange.201500250 |
| Abstrakt: | 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. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.) |
| Databáze: | MEDLINE |
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