69 DNA-binding studies of large antiviral polyamides |
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| Authors: | Elena Vasilieva Gaofei He Kevin J. Koeller G. Davis Harris James K. Bashkin |
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| Affiliation: | 1. Department of Chemistry &2. Biochemistry , Center for Nanoscience, University of Missouri-St. Louis , One University Blvd, St. Louis , MO , USA Phone: Phone: +1 (314) 516-4392 Fax: Phone: +1 (314) 516-4392 |
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| Abstract: | Polyamides are minor groove DNA-binding agents derived from the natural product distamycin A. PA1 is a large 12 ring polyamide discovered by NanoVir LLC; it is bioactive against the HPV16 virus in cell and tissue culture (Edwards et al., 2011). To better understand the basis of this phenomenon, the interactions of PA1 with the regulatory sequence of the HPV16 genome (7662–122?bp) are being examined. Using affinity cleavage as detected by capillary electrophoresis, with PA1 attached to methyl propyl ethidium iron EDTA, 10 binding sites of PA1 were identified in this part of the HPV genome. Polyamide perfect binding sites were as predicted by recognition rules (Dervan & Edelson, 2003). Quantitative DNaseI footprinting indicates that both perfect and single mismatch sites are bound with Kds in the low nm range. Interestingly, a wide range of Kds are observed for double mismatch sites (1–60?nm) and are under examination. This work will permit us to build a map of PA binding to HPV sequences, thus informing mechanisms of in vivo behavior. | |
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