Study On The Interaction Between Some Active Components In Chinese Traditional Medicines And Proteins

Protein serves as a transport carder for drugs,and the binding of drugs with protein has a great influence not only upon the distribution of the drugs in the body but also upon their patterns of metabolism and excretion.Further,from the standpoint of drug efficacy,only that portion of a drug that is not bound with plasma protein is generally bioactive.Thus,the study of the binding characteristics of medical drugs to protein is an important field in drug research.On the basis of the previous research, the interactions were carried out between protein and several active components of Chinese herbs using the fluorescence and UW/vis absorption spectroscopy.The thesis consists of six parts and the main conclusions are summarized as following.1.The status quo of drug molecules and biomacromolecules interaction was summarized briefly.The some methods in this research field were summarized,for example,fluorescence and UV/vis absorption spectroscopy,in order to obtain support of the theory for this thesis.2.The interaction between hesperidin or icariin and lysozyme(LYS) was studied by fluorescence spectroscopy in physiological buffer solution.It was observed that there was a strong fluorescence quenching reaction of hesperidin or icariin to LYS. The quenching constants of the drugs with LYS were measured at different temperature,and quenching mechanism was suggested as dynamic quenching for HES-LYS system and both static and dynamic quenching for ICA-LYS system.The thermodynamic parameters of the interactions indicated that the interaction between hesperidin and lysozyme was driven mainly by hydrophobic force,whereas the interaction between icariin and LYS was driven mainly by electrostatic force.The results of synchronous fluorescence spectra showed that binding of hesperidin or icariin to LYS induced conformational changes in LYS.3.Three flavones compounds possessed analogical structure(Chrysin,Apigenin and Morin) were selective as research targets.A combination of UV/vis,resonance light scattering(RLS),fluorescence polarization and synchronous fluorescence has been used to characterize the binding between threes flavones and bovine serum albumin(BSA) under physiological condition.Especially,the structure-performance relationship(SPR) in drug-BSA binding process was investigated detailedly.The results indicated that the interaction between drug and BSA was influenced by the structural variety of drug molecule.To flavone compounds,such acting groups in drug-BSA interaction,bearing the simultaneous functions of promoting and obstructing.4.The bioinorganic effects of four metal ions(Me²⁺),such as Ca²⁺,Mg²⁺,Zn²⁺, and Cu²⁺ on the interaction of threes flavone compounds with BSA were discussed.5.The participant manner and interferential mechanism of the other categories of adseititious reagents(I,NaNO₂,Glucose and VC) to the drug-protein binding were discussed.6.The fluorescence enhancement effect of arctiin was exploited for the first time to analyze the interaction with target protein as a probe by fluorescence spectroscopy, UV-visable spectroscopy and fourier transform infrared spectroscopy.The binding constants were obtained at different temperatures.In addition,the high value of fluorescence anisotropy suggested that the probe molecule is located in motional restricted environment of the protein.The thermodynamic function enthalpy and entropy for the reaction were calculated according to vant's Hoff equation,and the binding modes were also deduced.The effects of aretiin on protein second structure were studied by synchronous fluorescence spectra,three-dimensional fluorescence spectra and fourier transform infrared spectroscopy.The influences of some inorganic anions and cations on the drug-protein reaction system were also investigated.