Article
134 Large antiviral polyamide-DNA interactions
Journal of Biomolecular Structure and Dynamics
(2015)
Abstract
Polyamides are minor groove DNA binding agents derived from the natural product distamycin A. PA1 is a large 12 ring polyamide 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 (7348–122 bp) are being examined. Using an FeEDTA conjugate of PA1, 38 affinity cleavage (AC) patterns were detected for this fragment using capillary electrophoresis (CE). Quantitative DNase I footprinting analysis indicates that perfect sites bind PA1 with between 0.7 and 2.2 nM. Due to the density of sites, for single, double, triple and quadruple mismatch sites were characterized. These range from 1–3 to 20 nM. A limited single mismatch study of one PA1 site in the context of a 120mer indicates that the position of the substitution made no difference in affinity. Using AC and EDTA conjugates, we report that unlike smaller 8-ring hairpin PAs, introduction of a chiral turn in this large polyamide has no effect on binding orientation (forward vs. reverse). Studies of isolated PA1 sites by fluorescence spectroscopy and CE are also underway.
Keywords
- polyamides,
- DNA,
- antiviral
Disciplines
Publication Date
June 23, 2015
DOI
https://doi.org/10.1080/07391102.2015.1032767
Citation Information
Cynthia Dupureur, Elena Vasilieva, Yang Song, Kevin J. Koeller, et al.. "134 Large antiviral polyamide-DNA interactions" Journal of Biomolecular Structure and Dynamics Vol. 33 Iss. 1 (2015) p. 86 - 87 Available at: http://works.bepress.com/cynthia-dupureur/52/