纤溶活性化合物对蛋白质结晶特性影响的分析-analysis of the effect of fibrinolytic active compounds on protein crystallization characteristics.docxVIP

上海海洋大学硕士学位论文 III Investigation of Effects of Fbinolytic Compounds on Protein Crystallization Characteristics ABSTRACT Proteins are an essential part of biological process and are the basis of life itself. Determination of proteins’ three-dimensional structure by X-ray diffraction has an important role in understanding macromolecular structure, the mechanism of drug, the change or modification of molecular structure. Thrombotic disease is a major threat to human’s health; most of the clinical use of thrombolytic drugs such as heparin, abciximab, urokinase, there will be bleeding, allergic reactions, poor specificity, etc. Therefore, drugs which have the low risk of bleeding, do not damage the blood factors, the activity can be simply regulated need to occur. GDG and FGFC1 were low molecule weight compound extracted from marine organism, they had fibrinolysis enhancing effects. The premise of the protein structure analysis by X-ray diffraction is suitable single crystal, however, the high quality single crystal is difficult to determine. Hen egg white lysozyme (HEWL) has been widely researched as the template of the protein crystallization theory by crystallization scientists due to its stability, solubility and easy to crystallize. In this paper, HEWL was illustrated for crystallization behavior to research the effect of fibrinolytic compounds GDG and FGFC1 on crystallization characteristic and crystal structure of HEWL and fibrinolysis factors. Explore the mechanism of low molecule weight compounds action to high molecule weight proteins, the impact of small molecule drugs on protein, protein-protein interactions to build theory support for protein structure-function relationship and new thrombolytic drug. In the first chapter, the thrombotic diseases research progress, the mechanism of new thrombolytic drugs, the relationship between bio-pharmaceutical and proteomics and the determination of protein crystal structure by synchrotron radiation X-ray diffraction wer