Fluorescence Study On The Interaction Of Some Medicinal Molecules With Human Serum Albumin

Human serum albumin (HSA), the most important and abundant protein in human blood plasma, can widely bind many exogenous and endogenous compounds, then realize storage and transport of many molecules and metabolites. So it plays an important role in a variety of biological and pharmacological functions. The study of interactions between small-molecular drugs and protein may provide some information of the structural features that determine the therapeutic effectiveness of drugs, and also offer an important theoretical base on researching diagnosis and prevention of diseases, mechanism of human diseases and developments of new drugs and so on. The thesis consists of four chapters and its main content presented as follows:Chapter 1. The structures and functions of proteins were briefly introduced. The developments and methods used to study the interactions of small-molecular drugs with protein were summarized.Chapter 2. Studies on the interaction between diacerein and human serum albumin by fluorescence spectrometryThe interaction between diacerein and human serum albumin was studied by fluorescence spectrophotometry under physiological conditions. At 302 K and 311 K, the binding equilibrium constant KA and numbers of binding site n were calculated by using two methods, and the calculated results were compared in the work. The thermodynamic parameters obtained from measured datas show that the binding of diacerein to HSA involved hydrogen bond and van der Waals force. According to the theory of Forster energy transfer, the binding distance (r= 2.88 nm) and transfer efficiency of energy(E=0.2738) between diacerein and HSA were determined. The interaction of diacerein and human serum albumin can induce the structural change of human serum albumin by synchronous fluorescence spectrometry.Chapter 3. Studies on the interaction between caffeine and human serum albumin by fluorescence spectrometryThe interaction between caffeine and human serum albumin was studied by fluorescence spectrophotometry under physiological conditions. When the concentration range of caffeine was large, the method of fluorescence has been used to characterize the binding. The results of experiment datas indicate that caffeine under all concentrations (Ccaffeine/CHSA:30～200) can decrease the fluorescence of HSA by a static quenching procedure, however, with high concentration of caffeine (Ccaffeine/CHSA> 100), which followed by a dynamic quenching process. According to the figures of thermodynamic parameters, the acting force of between caffeine and HSA was hydrophobic force, with a spontaneous and exothermic chemical reaction. The studies of synchronous fluorescence spectra showed that caffeine can induce the structural change of HSA. The efficiency of Forster energy transfer can occur between the caffeine and HSA.Chapter 4. Studies on the interaction of theophylline and theobromine with human serum albumin by fluorescence spectrometryThe two drugs (theophylline, theobromine) with structural isomer were selected as research targets. When the concentration ranges of the two drugs were large, the methods of fluorescence have been used to characterize the binding between HSA and them under physiological conditions. The results of experiment datas indicate that under big concentrations (Cdrug/CHSA:30～200) they all can decrease the fluorescence of HSA by a static quenching procedure. However, with high concentration of the two drugs (Cdrug/CHSA> 100), they all followed by dynamic quenching processes. According to the datas of thermodynamic parameters, the acting forces of between two drugs and HSA were hydrophobic forces, with spontaneous and exothermic chemical reactions. The studies of synchronous fluorescence spectra showed that the two drugs can induce structural changes of HSA. The efficiency of Forster energy transfer all can occur between two drugs and HSA.