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

[Image: see text] 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.