Spectral And Molecular Modeling Method Studies On The Interaction Of Small Organic Molecules And Proteins

Proteins are the important living organisms, they are one of the most abundant components in cells and one of the most functional macromolecular in bodies, and play the role as drug carrier in delivering all sorts of endogenous and exogenous small molecules to each organ. The study on the conformation and function of proteins is useful not only for providing good clinical examination methods, but also for providing information on understanding of drugs transport and metabolism in the body. The research on the interaction between proteins and organic compounds such as drug is helpful to design and exploit new type of drug and offer the mechanism of drug action from the molecular level, etc. In the thesis, fluorescence spetrum, ultraviolet-visible spectrum and molecular modeling method are employed to study the interaction between drug and proteins. The paper consists of five chapters.In chapter 1, the study on the interactions of small drug and proteins using molecular spetrum were summarized.In chapter 2, the interaction between bovine serum albumin and hybrids of pyrimidine nucleoside pyrano with antiviral activity was studied by fluorescence and ultra-violet absorption spectroscopy, combined with molecular modeling method. The distance between donor and acceptor was calculated according to F?rster theory of non-radiation energy transfer. The synchronous fluorescence spectra displayed that hybrids changed the conformation of bovine serum albumin. Furthermore, using the molecular modeling method, the interaction between them was predicted from molecular angle. The results of molecular modeling analysis were in agreement with those of the experiments.In chapter 3, the interaction between pyrazolo[3,4-b]pyridinone derivatives and bovine serum album was studied in a simulated physiological conditions by fluorescence spectra and UV absorption spectra. By fluorescence quenching method and non-radiation energy transfer theory, the quenching mechanism was studied. The interaction forces between derivatives and bovine serum albumin were discussed according to the thermodynamic parameters. The structure changes of bovine serum albumin in the presence and absence of derivatives were discussed. The impact of metal ions on the binding reaction was investigated.In chapter 4, the interaction mechanism of bovine serum albumin and human serum albumin with repaglinide were investigated by fluorescence spectroscopy and UV absorption spectrometry. The structure change of serum albumin in the presence and absence of repaglinide were studied. Furthermore, using the molecular modeling method,the interaction between human serum albumin and repaglinide was predicted from molecular angle.In chapter 5, the interaction of bovine serum albumin with 5-hybrid-2′-deoxy uridine derivatives were investigated by spectrometry in physiological condition (pH 7.4). The mechanism of the interaction was discussed. The impact of metal ions on the binding reaction was investigated.The conformational change of bovine serum albumin was dicussed with the additon of derivatives by synchronous fluorescence spectroscopy. The results of molecular modeling suggest derivatives might locate in the Site I of human serum albumin.