DNA Binding Thermodynamics and Site Stoichiometry as a Function of Polyamide Size.

DNA Binding Thermodynamics and Site Stoichiometry as a Function of Polyamide Size. Biochimie. 2019 Jul 31;: Authors: Song Y, Niederschulte J, Bales KN, Park AH, Bashkin JK, Dupureur CM Abstract The interactions of 6-8 ring hairpin polyamides (PAs) with the minor groove of DNA have been investigated extensively. More recent studies of large antiviral PAs (14-20 rings) active against small DNA tumor viruses lead to questions regarding the extent to which the DNA binding behaviors of the well studied, smaller PAs can be reliably extrapolated to the larger ones. Described here is the first reported study of hairpin PA-DNA binding thermodynamics as a function of PA size (6 to 20 rings). All PAs exhibit binding affinity in the low nM to upper pM range, which indicates that affinity is not a discriminator of antiviral activity. Unlike the smaller PAs, a 20-ring PA does not appreciably dissociate from DNA in competition experiments, which indicates very long residence time that is consistent with antiviral activity (the smaller PAs are inactive against human papillomavirus, HPV). While the DNA binding thermodynamics for the smaller antivirally inactive 6- and 8-ring PAs is clearly enthalpically driven, the larger antiviral PAs (14- and 20-rings) exhibit strongly entropically-driven DNA binding. These distinct energetic signatures indicate that different types of interactions drive these associations. In DNA binding site stoichiometry experim...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research