Abstract

Investigation of the Mechanism of Binding of Anticancer Drugs to DNA using ESI-MS

David Harman, Lecturer and Mass Spectrometry Facility Manager , University of Western Sydney

We strive to develop anticancer drugs of high activity, with low toxicity to normal cells.  In order to accomplish this, we attempt to thwart the propensity of cancer cells to undergo rapid division.  By developing organometallic platinum based drugs which intercalate strongly within the grooves of the telomeres of cancer cell DNA, telomerase activity can be arrested.  Without continual extension of the telomere lengths, immortality is defeated and cancer cells then proceed to programmed cell death.  In this study, we have measured by ESI-QToF-MS the degree of binding of a series of organometallic complexes to quadruplex DNA, a motif discovered within telomeres.  The results allow us to establish a structure/activity relationship, shedding light upon the mechanism of binding and providing valuable information to aid design of the next generation of anticancer therapeutics.