What is it about?

We have long noted the failure of our antiviral polyamides to follow the reported "rules" of DNA recognition. Here, we supply the explanation: enthalpic contributions to the binding constant do not occur productively and counterbalance the effects of entropy. Entropy is the only reason for a negative Gibbs free energy of binding. Also, these large polyamides follow trends reported but not commented on with smaller minor-groove binding compounds: they achieve much higher than 1:1 binding stoichiometries.

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Why is it important?

The broad-spectrum activity of our compounds against small DNA tumor viruses, including HPV16, 18, and 31, and three types of polyomavirus, is undoubtedly assisted by their ability to bind viral DNA regardless of sequence. However, the lack of cellular and tissue culture toxicity, and animal toxicity in initial safety studies, is explained in part by the recent report that AT-rich HIV chromatin is a much better target for minor groove binding drugs than human chromatin (10.1371/journal.pone.0216515). All the target viruses have AT-rich DNA.


The field of polyamide-DNA binding thermodynamics, and also binding kinetics, is just now beginning to be understood in its entirety. The current results add new perspectives and data to what was once considered a closed book. We look forward to providing more evidence and explaining more about how these molecules function, breaking down old paradigms that hinder progress.

Professor James Keane Bashkin
University of Missouri-St. Louis

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This page is a summary of: DNA binding thermodynamics and site stoichiometry as a function of polyamide size, Biochimie, October 2019, Elsevier, DOI: 10.1016/j.biochi.2019.07.021.
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