| As dammarane tetracyclic triterpenoids natural products, 20(S)-Protopanaxatriol is an ocotillol which is extracted from Panax, ginseng or American ginseng and other plants. Studies have shown that PPT has a broad biological activity, such as anti-fatigue, antioxidant anti-aging, regulating blood sugar, improving cardiovascular and cerebrovascular insufficiency and regulating the central nervous system and so on. Furthermore, PPT can inhibit tumor cell proliferation and promotes tumor cell apoptosis and induce tumor cell differentiation and other anti-tumor activity. With significant anti-tumor cell activity and toxic side effects, PPT attracted wide attention of domestic and foreign scholars because it was a good anti-tumor drug candidates. However, the low bioavailability and poor water solubility of PPT have limited their application in antitumor drug. Cyclodextrin and its derivatives(β-CDs) could improve the poor water solubility and low bioavailability of drug molecules due to its characteristic of inner hydrophilic and outer hydrophobic, which can form supramolecular systems with drug molecules. In recent years, there are arousing researches about utilizing cyclodextrin to mediate the solubility of drug and the study of supramolecular chemistry has become a research hotspot. Study the characteristics of small drug molecules interact with proteins can help us understand the mechanism of action between them from the molecular level, which is of great significance in promoting proteomics, pharmacology and toxicology research and so on. Bovine serum albumin(BSA) was selected as a template to study the interaction between protein and drugs because of its similarity to human serum albumin(HSA) and easy accessibility. The transport and metabolism of the drug in the body at the molecular level would be understood through studying the interaction of supramolecular systems and BSA. Experiment combined with computational simulation is a common method to study the mechanism between protein and drug molecules.It can provide more information, such as studying the binding mechanism between protein and small moleecules, that using computational simulation.The binding mechanism can be quantitatively validated by spectrum experiment. Experiment combined with computational simulation, not only improve the accuracy of the research, but also provide more available information for the research on the mechanism of ligand-protein. Therefore, the study of drug molecules interact with proteins has become more and more popular.In this paper, seven kinds of modified β-CDs were synthesized, and seven kinds of modified β-CDs/PPT supramolecular systems were prepared and characterized. Then speculate on its possible binding mode. Besides, fluorescence spectrometry and computational simulation were used to study the interaction between supramolecular system and bovine serum albumin(BSA).The major content of this thesis are as follows:1. Seven kinds of modified β-CDs(hosts 1-7) were synthesized and characterized.2. Four kinds of modified β-CDs/PPT(hosts 1-4) supramolecular systems were prepared and characterized by a series of instruments, such as 1H NMR, SEM, XRD, IR and so on. The possible binding mode of hosts 1-4 and PPT was speculated according to the 2D ROESY. At the same time, the method of theoretical computer simulation used to verify the binding mode of host 4/PPT. Results showed that the experimental results were corresponding to the theoretical simulation. UV titration show that the binding stoichiometry between hosts 1-4 and PPT was 1:1 and stability constant increased in the following order: K4/PPT>K2/PPT>K3/PPT>K1/PPT. Result of saturated water solution experiments showed that water solubility of PPT increased 1927, 2649, 4525 and 5932 times after the formation of supramolecular system, respectively. Host 4 solubilization effect is the best.3. The interaction between hosts 1-4/PPT supramolecular systems and BSA was studied by fluorescence quenching technique and ultra-violet absorption spectroscopy. Results indicated that host 1-4/PPT supramolecular systems led to the intrinsic fluorescence quenching of BSA through a static quenching process. Electrostatic force was as the main driving force to form the 1:1 compounds. The result of synchronous fluorescence spectra shows that binding of host 1-4/PPT supramolecular systems with BSA could induce conformational changes in BSA, which the part of tryptophan changed. However, the dipole-dipole non-radiative energy transfer is another reason which causes BSA fluorescence quenching occurs.4. Supramolecular systems of the guest PPT with three kinds of bis(CD)s had been prepared and characterized. Three possible binding modes of bis(CD)s with PPT were analyzed by 2D ROESY. UV-visible spectroscopy experiment shows that the binding constant increased in the following order: K6/PPT>K5/PPT>K7/PPT, and the binding sites were close to unity. Besides, water solubility of PPT increased 790, 1611, 623 times after PPT was packaged by bridging cyclodextrins, respectively. Studying the interaction mechanism between supramolecular system hosts 5-7/PPT and BSA, that hosts 5-7/PPT and BSA could strongly quench the intrinsic fluorescence of BSA by static quenching. Electrostatic force was as the main driving force to form the 1:1 compounds.Furthermore, with the addition of supramolecular systems, the tryptophan residue of BSA changed.5. The interaction mechanism of PPT and BSA was investigated by fluorescence spectrometry and ultra-violet absorption spectroscopy. Compared with the mechanism of supramolecular systems/BSA, the force between PPT and BSA, the binding stability constant Kb and BSA conformation was changed, because of the presence of hosts 1-7. But the number of binding sites n unchanged. Comparative the binding stability constant, and discovery that KPPT/BSA> K1-7/PPT, it shows that BSA can seize the PPT which included in the seven kinds of supramolecular systems through competitive inclusion.6. Molecular docking and molecular dynamics simulations were performed to study the mechanism of the host 4/PPT supramolecular systems and PPT/BSA. The calculation results show that their binding mode, binding sites, the force and its effect on the conformation of BSA are consistent with experimental results.
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