PA1 is a large 14-ring polyamide that is active against HPV16 in cell culture (Edwards, T. G.; et al., Antivir. Res. 2011, 91, 177�186.).  To better understand the basis of this antiviral activity, we have undertaken biophysical studies of its DNA binding behavior.  Using both hydroxyl radical and DNaseI footprinting detected by capillary electrophoresis, we have characterized a number of low nM binding sites in the HPV16 genome. Polyamide binding orientations are obtained by using affinity cleavage and a PA tethered to iron EDTA .  Using a simple fluorescence binding assay, we have also demonstrated that while affinity is poor in the absence of additives, low nM affinity for a short cognate DNA hairpin is consistently observed in the presence of a wide variety of additives and more closely matches affinities obtained via footprinting on a long DNA.

DNA binding properties of a large antiviral polyamide via capillary electrophoresis

243rd National Meeting (2012)

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