Studies On The Interactions Between Amino Phosphine Ester Derivatives With CtDNA

Deoxyribonucleic acid (DNA) is the basic genetic material of life; it plays a vital role in phenomenon of all life. To clarify the interaction between DNA and small molecules, ions and protein, especially the interaction of DNA and small molecules is the important research topic in the clinical, life science and pharmaceutical chemistry. Because it can provide a reasonable explanation for the interaction of DNA and protein and the mechanism of anticancer drugs, and provide guidance information for the design of new efficient anti–cancer drugs.α–amino phosphate ester has the similar structure toα–amino acids. It is an important role of organic phosphorus chemistry in recent decades. It is found thatα–amino phosphate ester has anticancer, antioxidant activity, antitumor, bactericidal and resistance to plant viruses'activity. Many researchers committed to remodify the whole framework ofα–amino phosphate to synthesize new compounds through the introduction of the special nature of the atom or change the structure ofα–carbon, phosphorus and amine. They hoped that they can research new drugs which have anti–cancer and less poisonous through the modification of the structure.In this paper, the interaction of derivatives ofα–amino phosphate ester PPAP, NMAP, HMPAP and NPAP with ctDNA have been investigated by UV spectra, fluorescence spectra, molecular modeling and isothermal titration calorimetry (ITC). The binding constant (Kb) and the binding stoichiometry (n) of PPAP, NMAP, HMPAP and NPAP to ctDNA at different temperatures were calculated from fluorescence spectra and discussed the possible binding mode combination of UV spectra respectively. The combination pattern of the interactions between four derivatives and ctDNA were obtained from molecular modeling, and the results indicated that they can slide into the G–C rich region of ctDNA. The molar enthalpy change for the binding (?H0), the binding stoichiometry (n) and the binding constant (Kb) were obtained from ITC, and the entropy change and free energy change of the binding were calculated; according to the magnitude of enthalpy change and entropy change, we determined the mainly intermolecular force. It is found that the interaction between ctDNA and PPAP and NMAP is stronger than that between the HMPAP and NPAP.We induce that the different substituents of benzene affect the interaction between derivatives and ctDNA. The results may provide theory and experiment basis for reference of the interaction mechanism forα–amino phosphate ester derivatives in organisms, and these studies are expected to provide guidance into the design of new amino phosphate ester drugs.