We study the spatiotemporal control of the activity of biologically active compounds. In our current studies we put applications in which DNA or RNA are used as control elements under the control of light as a trigger signal. Nucleic acids as well as their derivatives and analogues can be used for a variety of applications ranging from gene regulation (RNA interference, antisense strategy etc.) over the modulation of protein function (for example with aptamers) to molecular diagnostics and beyond. Furthermore light is an ideal trigger signal which can be used for addressing single cells in thin tissues or small organisms. With light microscopes it is possible to visualize the specimen of interest while irradiating certain areas with spatiotemporal and dosage control. Our goal is for example to answer questions in developmental biology via the spatiotemporal gene regulation through light.
Our research is located right at the interface between chemistry and biology/medicine as well as physics with organic synthesis as our central element. The methods we use range from organic synthesis on "flask-scale" over automated and manual solid phase synthesis, MPLC, HPLC, the full scale of characterization methods to biochemical and molecular biological procedures, cell culture and microscopy including nonlinear optics as well as atomic force microscopy.
Fig. 01: "Caged" compounds are molecules which can control biological activity that have been made temporarily inactive. By irradiation with light the activity and hence the biological process can be restored with precise control of space, time and intensity. The term "caged" must be understood figuratively. In reality the blocking principle is a suitable photolabile group at a position important for the compound's activity.
Even though DNA offers no tertiary interactions it is a very interesting material for nanotechnology. It is a relatively cheap, well-characterized macromolecule which is programmable and can be manipulated with a big toolbox of chemical and molecular biological methods.
We are exploring new interaction modules for DNA nanoarchitectures that go beyond the Watson-Crick base pairing. For example we are using molecules that can sequence-specifically bind to DNA. In the simplest approach two of these Dervan-type polyamides are connected to form a "DNA-strut" which can act as second, orthogonal structural element (besides the Watson-Crick interaction). In a figurative sense these DNA-struts can be seen as sequence-selective glue for DNA origami.
Fig. 02: DNA minicircles are held together sequence-specifically by "DNA anchors" with DNA-binding polyamides.