High DNA affinity of a series of peptide linked diaromatic guanidinium-like derivatives.

In this paper we report the design and synthesis of a new family of asymmetric peptide linked diaromatic dications as potent DNA minor groove binders. These peptide-linked compounds, with a linear core, displayed a much larger affinity than other guanidinium-like derivatives from the same series with curved cores. As a first screening, the DNA affinity of these structures was evaluated by means of thermal denaturation experiments, finding that the nature of the cation (guanidinium vs 2-aminoimidazolinium) significantly influenced the binding strength. Their binding affinity was assessed by implementing further biophysical measurements such as surface plasmon resonance and circular dichroism. In particular, it was observed that compounds 6, 7, and 8 displayed both a strong binding affinity and significant selectivity for AT oligonucleotides. In addition, the thermodynamics of their binding was evaluated using isothermal titration calorimetry, indicating that the binding is derived from favorable enthalpic and entropic contributions.