Investigations Of The Interaction Between Drugs And Protein By Spectroscopic And Molecular Modeling Methods

Protein relate closely with life and various vital activities. It participates in the conformation of cells and the activities of organism. Therefore there is no life without protein. Serum albumin, which is the most abundant carrier protein in blood plasma, can bind with many drug molecules. The binding of drugs with serum albumin directly affects not only the absorption, distribution and metabolism of drug, but also the drug efficacy. Therefore, the studies on the interaction between drugs and protein have been an important project in the field of biochemistry, toxicology, pharmacology and pharmacokinetics.Fluorescence and UV absorption spectroscopic methods have been widely used because of their convenience, rapidity, sensitivity and so on. Molecular modeling technique can vividly show the result of the interaction of drugs with protein. In the thesis, the interactions between drugs and protein were studied by spectroscopic and molecular modeling methods. This dissertation consists of five chapters:Chapter 1: The significance, status, and prospect of the investigation on the interactions between drugs and protein were briefly illustrated, and the principles of spectroscopic and molecular modeling methods were also explained.Chapter 2: The interaction between bovine serum albumin (BSA) and one of pyrano [4,3-b] pyran derivative was investigated by fluorescence and molecular modeling methods in physiological condition. According to the data of fluorescence spectra, the binding constants, force and distance were calculated. The effect of this derivative on the conformation of BSA was analyzed by the synchronous and three-dimensional fluorescence spectra techniques. Human serum albumin (HSA), instead of BSA was used in molecular modeling method, and the possible binding site was predicted.Chapter 3: In simulative physiological condition, the interaction of a pyrano [3,2-c] pyridine-5 -ones derivative with BSA was studied. The quenching mechanism was judged by fluorescence and UV absorption spectroscopic methods, and the binding force, distance and the effect of some metal ions were also calculated. The synchronous and three-dimensional fluorescence spectra methods were used to discuss the influence of this derivative on the conformation of BSA. The possible interaction region of this derivative with HSA was analyzed by molecular modeling method.Chapter 4: The interaction between ambroxol hydrochloride and HSA was investigated. The quenching mechanism was explored by fluorescence and UV absorption spectroscopic methods, and the possible interaction site of them was forecasted by molecular modeling method from molecular angle.Chapter 5: The interaction of fenofibrate and HSA was investigated in pH 7.4 condition. The characterization of their interaction was studied using spectroscopic methods, and the possible binding site was predicted using molecular modeling method.