The path for metal complexes to a DNA target
The discovery of cisplatin as a therapeutic agent stimulated a new era in the application of transition metal complexes for therapeutic design. Here we describe recent results on a variety of transition metal complexes targeted to DNA to illustrate many of the issues involved in new therapeutic design. We describe first structural studies of complexes bound covalently and non-covalently to DNA to identify potential lesions within the cell. We then review the biological fates of these complexes, illustrating the key elements in obtaining potent activity, the importance of uptake and subcellular localization of the complexes, as well as the techniques used to delineate these characteristics. Genomic DNA provides a challenging but valuable target for new transition metal-based therapeutics.
© 2013 The Royal Society of Chemistry. Received 8th January 2013, Accepted 8th February 2013. First published online 20 Feb 2013. We are grateful to the NIH (GM33309) for their support of this research.
Published - c3cc00177f.pdf