Nucleic Acids Chemistry
Nucleic acids and linker chemistries are important to expand the functional range of DNA strands. For example, fluorophores are chemically attached to facilitate the detection of DNA. The Howorka group has created new nucleotide derivatives which enable the facile and highly efficient labelling of DNA strands with fluorophores and several other biotags (1-3). The linker chemistry under mild conditions involves e.g. Diels Alder reaction.
In addition, we have developed linker and surface chemistries which enable the immobilisation of DNA and other molecular receptors onto sensor surface and biophysical research platforms. The key benefit is the retention of the receptors’ specific recognition activity for analytes. At the same time, the sensor surface is rendered resistant to the undesired adsorption of non-target molecules. Different linker chemistries have been successfully used including poly(ethylene glycol) but also molecularly defined DNA nanostructures resembling a tetrahedron (see illustration) (4,5). In microarrays, this dual advantage has achieved the ultrasensitive sensing of diagnostically important RNA species which remain undetected in conventional analytical schemes (6). As further highlight, epigenetically relevant methylated DNA strands could be analysed at the single-molecule level in collaboration with Prof. Hinterdorfer as published in Nature Nanotechnology (7).
(1) V. Borsenberger, S. Howorka, Nucleic Acids Res. 2009, 37, 1477-1485.
(2) V. Borsenberger, M. Kukwikila, S. Howorka, Org. Biomol. Chem. 2009, 7, 3826 - 3835.
(3) V. Borsenberger, N. Mitchell, S. Howorka, J. Am. Chem. Soc. 2009, 131, 7530-7531.
(4) R. Schlapak, J. Danzberger, D. Armitage, D. Morgan, A. Ebner, P. Hinterdorfer, P. Pollheimer, H. J. Gruber, F. Schaffler, S. Howorka, Small 2012, 8, 89-97.
(5) N. Mitchell, R. Schlapak, M. Kastner, D. Armitage, W. Chrzanowski, J. Riener, P. Hinterdorfer, A. Ebner,S. Howorka, Angew. Chem. Int. Ed. 2009, 48, 525-527.
(6) S. Howorka, J. Hesse, Soft Matt. 2014, 10, 931-941.
(7) R. Zhu, S. Howorka, J. Proll, F. Kienberger, J. Preiner, J. Hesse, A. Ebner, V. P. Pastushenko, H. J. Gruber, P. Hinterdorfer, Nat. Nanotechnol. 2010, 5, 788-791.