Toroidal, or ring-shaped, proteins are used in a variety of ways by the cell. Almost all classes of enzymes involved in DNA metabolism have a toroidal motif that is central to their function.

An example of a toroidal protein known as the DNA sliding-clamp is a key subunit of the DNA polymerase holoenzyme complex, the central enzyme of DNA replication.

A key feature that characterises the structure of toroidal DNA-binding proteins such as the DNA sliding clamp is the central cavity (~ 35 Å) which is large enough to accommodate B-DNA (~ 20 Å diameter).

In general, the DNA-protein interaction is purely topological and it is greatly stabilised by powerful electrostatic interactions between the polyanionic phosphodiester backbone of DNA and a region of high positive potential that surrounds the inner surface of the toroid.

In this research program, we have sought to answer whether linear DNA can thread nanoscale cationic macrocycles of platinum that we have termed DNA Nanoshuttles. The interaction of nanoscale platinum complexes with DNA is unprecedented and it would represent a significant advance in the field of metal-DNA chemistry.

As a direct consequence of the nanoscale dimensions, shape and charge that allow the DNA Nanoshuttles to interact with DNA in a topological manner, there exists the exciting possibility of developing them into electrostatic models of toroidal DNA-binding proteins and a new class of synthetic probes of DNA structure and function.

Furthermore, it is feasible that DNA Nanoshuttles may eventually find useful applications in the rapidly developing field of "DNA nanotechnology".

Group members currently involved in this project include Dr Clodagh Mulcahy and David Schilter.

This project is a collaboration with Prof. Margaret M. Harding (UNSW) and Dr. Jen Bodkin (UNSW).

Selected Publications

Conference Presentations

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