Radiosensitization by DNA, Binding Pyrrole, Imidazole Polyamides

Pyrrole (Py) - Imidazole (Im) polyamides are a class of non-genotoxic DNA-binding small molecules with modular sequence recognition and high affinity. A polyamide targeted to the sequence 5'-WGWWCW-3', corresponding to the Androgen Receptor (AR) Response Element (ARE) half-site, suppresses AR positive prostate tumor xenografts. Evidence for inhibition of DNA dependent processes including allosteric inhibition of AR-DNA interactions and RNA Polymerase II transcription are observed in vitro. It is hypothesized that polyamides may displace DNA repair elements recruited after genotoxic insult and thereby sensitize cells to ionizing radiation.