Spectroscopic and Simulation Studies of the Sequence-Dependent DNA Destabilization by a Fungicide.

The understanding of the structural change of DNA induced by fungicides is essential as the non-targeted action of fungicides causes genotoxicity, leading to several serious diseases such as cancer, behavioral change, and nausea. In this study, the binding of an important fungicide, namely, n-dodecylguanidine acetate (dodine), with B-DNA having different sequences of nucleobases and its effect on the structure of B-DNA has been investigated using spectroscopic and simulation methods. In general, the addition of dodine destabilizes DNA; however, the binding of dodine causing the destabilization of DNA is highly sequence dependent. In the case of adenine(A)-thymine(T)-based DNA, dodine intrudes into the minor groove of DNA and interacts with the A-T bases mainly through its hydrocarbon tail, which destabilizes the stacking interaction of the flanking bases. In contrast, the polar group of dodine interacts with guanine(G)-cytosine(C)-rich DNA, and the interaction is dynamic as it shuttles between the minor groove and terminal regions. The binding of dodine with G-C-rich DNA affects the stacking interaction of the terminal base regions specifically. This study reveals the base-specific binding mode of dodine, which causes destabilization of the duplex DNA.