The Interaction Between Quinolone Antibiotics And Bovine Lactoferrin, Human Serum Albumin

The researching field of the protein is an important project in many researching area such as biology, clinical medicine, medical chemistry, chemistry and so on. Especially in the field of the interaction between protein and some drug molecules, exploring those mechanisms not only helps us to understand the reactions between the protein and the small molecules at the molecular level, but also helps us to understand the pharmacology and toxicology of the durgs and shows a good direction to the drug molecules design and exploitation of the new drugs. In this thesis, the author used the Bovine Lactoferrin (BLf), Human Serum Albumin (HSA) and four drugs of quinolone antibiotics as research objects. Based on the site binding model of the bio-macromolecules with small molecules, the author applied the technologies of the spectroscopy and microcalorometry and studied the interaction mechanisms between the Bovine Lactoferrin or Human Serum Albumin and some kind of drugs of quinolone antibiotics such as Ofloxacin, Gatifloxacin, Lomefloxacin, Pefloxacin Mesylate and so on.In the part of spectroscopy analysis, the binding characteristics and mechanism of quinolone antibiotics to Bovine Lactoferrin or Human Serum Albumin have been investigated by using the fluorescence quenching property of the drugs to the protein. The equilibrium constants and number of binding sites for these quinolone drugs in this research interacting with BLf or HSA are measured by fluorescence method. The transfer efficiency of energy and distance between these drugs and BLf or HSA areobtained according to the mechanism of Forster-type dipole-dipole nonradiative energy-transfer. The effect of each drug on the conformation of BLf or HSA was also been analyzed by using synchronous fluorescence spectroscopy. The spectroscopy analysis shows that all those quinolone drugs can react with BLf or HSA and form a drug-protein compound. Furthermore, all of those drugs can affect the configuration of the two protein.In the part of the thermodynamics, the thermodynamic function of the reaction of quinolone drugs non-covalence binding with BLf or HSA are determined by using microcalorimetry technology. Microcalorimetry analysis results show that in the reaction between Gatifloxacin and BLf or HSA, the molar change of enthalpy is aboutA rHm=0. The reaction between Gatifloxacin and BLf or HSA is entropy-driven modeland the main binding force is hydrophobic interaction.