Spectral Study On The Interaction Of Several Small Molecule Drugs And Proteins

The protein is essential for the life process and plays an important role in metabolizing of cells.Serum albumin is the most abundant protein in the body.As its combination with drugs,serum albumin has many important physiological functions and pharmacology.Therefore,the development of small molecule research,particularly the research on the interaction mechanism of between of a small molecule with biological activity and protein is very important for the development of new medicines.And it is also a topic of common concern and interest in life sciences,chemical and clinical.Based on the work of our predecessors, the interact mechanism of between small molecule drugs and protein and the effect of drugs on portion were studied by using fluorescence spectroscopy,UV-visible absorption spectroscopy,and Fourier transform infrared spectroscopy.The studies in this thesis are summarized as follows:1.The methods such as UV-vis,FTIR and fluorescence spectroscopy were used for research,through which the reactions between medicine and protein and the progress in pharmaceutical analysis in recent years were reviewed.And the idea of the study was proposed.2.The binding reactions between furbenicillin sodium(FBS)and bovine serum albumin(BSA)under physiological condition was investigated with fluorescence spectroscopy,UV-visible absorption spectroscopy and Fourier transform infrared spectroscopy.The results showed that a strong interaction of FBS with BSA was found and the fluorescence quenching function of FBS to BSA was observed.The binding constants and binding sites of FBS and BSA under different temperatures were obtained with Stern-Volmer equation and double logarithmic equation analysis,which is 1.04×10⁴L mol^-1and 1.09 at room temperature(26℃),respectively.Infrared spectra showed that the secondary structure was changed by the interaction between FBS and BSA.3.The interaction between human serum albumin(BSA)and nobiletin (NOB)and its thermodynamic characteristics were investigated by multi-spectroscopy in physiological medium.The results showed that NOB could quench the fluorescence of BSA with a static quenching mechanism.The apparent binding constant and the number of binding sites were estimated as 3.25×10⁴ L mol^-1and 1.24 for BSA-NOB at 294 K with Stern-Volmer equation and double logarithmic equation analysis. The binding constant of NOB and BSA was estimated as 2.73×10⁴ L mol^-1at room temperature Using UV spectra,which is similar to that obtained by fluorescence analysis,while the thermodynamic parametersâ–³H andâ–³S were estimated as 55.91 kJ·mol^-1and 276.5 J·mol^-1·K^-1, which indicated that the interaction force of the NOB and BSA is the main hydrophobic force.The fluorescence quantum yield of BSA was calculated as 0.074 using reference method.According to Forster theory, the energy transfer efficiency and the interaction distance of BSA and NOB were given as 0.274 and 1.76 nm.Synchronous fluorescence spectra of HSA indicated that the conformations of BSA were not changed in presence of NOB.4.Multiple spectroscopes were employed to investigate the interaction between Huperzine A(HA)and HSA in physiological conditions.A strong fluorescence quenching phenomena of HSA by HA was observed. The research results showed that the interaction is a static quenching process concomitance with energy transfer.The binding constants and binding site(K)at different temperatures were investigated and the results showed that the value of K decreased with the increase of the temperature.The interaction force between HA and HSA can be determined as electrostatic attraction force based on the changes of reaction enthalpy and entropy.The distance and energy transfer efficiency were also calculated based on irradiative energy transfer mechanism.