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.
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