Chemo-Genetic Optimization of DNA Recognition by Metallodrugs using a Presenter-Protein Strategy

Zimbron, Jeremy M. and Sardo, Alessia and Heinisch, Tillmann and Wohlschlager, Therese and Gradinaru, Julieta and Massa, Claudia and Schirmer, Tilman and Creus, Marc and Ward, Thomas R.. (2010) Chemo-Genetic Optimization of DNA Recognition by Metallodrugs using a Presenter-Protein Strategy. Chemistry - A European Journal, 16 (43). pp. 12883-12889.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A5841542

Downloads: Statistics Overview


The mode of action of precious metal anticancer metallodrugs is generally believed to involve DNA as a target. However, the poor specificity of such drugs often requires high doses and leads to undesirable side-effects. With the aim of improving the specificity of a ruthenium piano-stool complex towards DNA, we employed a presenter protein strategy based on the biotinavidin technology. Guided by the X-ray structure of the assembly of streptavidin and a biotinylated piano-stool, we explored the formation of metallodrug-mediated ternary complexes with the presenter protein and DNA. The assemblies bound more strongly to telomere G-quadruplexes than to double-stranded DNA; chemo-genetic modifications (varying the complex or mutating the protein) modulated binding to these targets. We suggest that rational targeting of small molecules by presenter proteins could be exploited to bind metallodrugs to preferred macromolecular targets.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Schirmer)
05 Faculty of Science > Departement Chemie > Chemie
05 Faculty of Science > Departement Chemie > Chemie > Bioanorganische Chemie (Ward)
UniBasel Contributors:Creus, Marc and Schirmer, Tilman and Ward, Thomas R. R.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:24 Apr 2017 10:18
Deposited On:14 Sep 2012 06:37

Repository Staff Only: item control page