Control of DNA structure by synthetic metallomolecules
Synthetic metallomolecules can be designed so that they bind to DNA resulting in changes to the strucutre of DNA which leads to a loss of functionality. We have been developing synthetic transition metal complexes which have been shown in vitro to have a significant effect on DNA, in some cases promoting dramatic supercoiling.
The class of molecule includes self assembling supramolecular helicates and those with a transport motif linked to a DNA binding motif. We are developing optical techniques including circular dichroism, linear dichroism and light scattering as well as mass spectrometry, bioimaging and electrophoresis as tools to discover the precise mechanisms by which these molecules have such an effect.
AFM images demonstrating the DNA supercoiling induced by the addition of one of the supramolecular metallomolecules
A.D. Richards and A. Rodger, Synthetic metallomolecules as agents for the control of DNA structure, Chem. Soc. Rev., 2006, doi:10.1039/b609495c
M.J. Hannon, V. Moreno, M.J. Prieto, E. Molderheim, E. Sletten, I. Meistermann, C.J. Isaac, K.J. Sanders and A. Rodger, Intramolecular DNA coiling mediated by a metallo-supramolecular cylinder, Angew. Chem., Intl. Ed., 2001, 40, 879-884