Exploring the binding mechanism of phosphoramidate derivative with DNA: spectroscopy, calorimetry and modeling

In this study, one of the amino phosphine ester derivatives α-(3-hydroxy-4-methoxyphenyl)-N-phenyl-α-aminophosphonate (HMPAP) was synthesized, and the molecular interaction of HMPAP with ct-DNA has been investigated by UV-Vis absorption spectra, fluorescence spectra, isothermal titration calorimetry (ITC) and molecular modeling. The binding constant (K(b)) of HMPAP to ct-DNA at different temperatures were calculated from fluorescence spectra. According to the UV-Vis absorption spectra, ethidium bromide displacement studies and ITC experimental results, we can conclude that HMPAP is an intercalator. The molecular modeling results indicated that HMPAP can slide into the G-C rich region of ct-DNA. ITC data showed that ct-DNA/HMPAP binding is enthalpy controlled. Furthermore, the results obtained from molecular modeling corroborated the experimental results obtanied from spectroscopic and ITC investigations.