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Organic Chemistry

Tutor Prof. Ing. Michal Hocek, CSc. DSc.

Michal Hocek

Topic Modifications of DNA by transition metal complexes and development of moleculat scissors for gene therapy

Oligonucleotides bearing transition metal complexes (capable of cleaving phosphodiester bonds in DNA) will be prepared by polymerase incorporations of modified nucleoside triphosphates or by chemical synthesis. They will be then studied in specific cleavage of dsDNA by triplex formation and eventually developed as molecular scissors in gene therapy and gene surgery (gene repair). Part of the work will be done in collaborating group of Dr. A Kellett at DCU Dublin. This project is supported by ITN project ClickGene from EU. The rules only allow hiring of students from outside of the Czech Republic (who have not beeing living here for more than 12 months in the last 5 years).

Leading references:
1. Vrábel, M.; Horáková, P.; Pivoňková, H.; Kalachová, L.; Černocká, H.; Cahová, H.; Pohl, R.; Šebest, P.; Havran, L.; Hocek, M.; Fojta, M. "Base-modified DNA labeled by [Ru (bpy)3] 2+ and [Os(bpy)3] 2+ complexes: construction by polymerase incorporation of modified nucleoside triphosphates, electrochemical and luminescent properties, and applications" Chem. Eur. J. 2009, 15, 1144-1154.
2. Vaníková, Z.; Hocek, M. "Polymerase Synthesis of Photocaged DNA Resistant against Cleavage by Restriction Endonucleases" Angew. Chem. Int. Ed. 2014, 53, 6734-6737.