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 (Kb) 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.

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► Medically important phosphoramidate derivative HMPAP is synthesized.
► HMPAP is intercalative binding into ctDNA helix.
► Hydrogen bonding may play an essential role in the binding of HMPAP with ctDNA.
► This binding interaction is predominantly enthalpy driven.