Study On The Interaction Between Pcbs And Human Serum Albumin

PCBs as persistent organic pollutants attract international extensive concerns and studies in term of carcinogenicity, nerve toxicity, endocrine disruption. Human Serum Albumin (HSA) is the most abundant carrier protein in blood circulation. It has many important physiological and pharmacological functions, which can bind many exogenous and endogenous ligands in blood, and maintenance osmotic pressure balance in colloid. Therefore, it has been model protein of most extensively studied of interaction between biological macromolecules and organic molecules. When PCBs enters into the body, it binds to HSA for impacting on distribution and metabolism in blood. The interactions between PCBs and HSA determine the mechanism of biological toxicity. Investigating the binding mechanism of organic pollutants, toxic materials and drugs with has many values in toxicology and pharmacokinetics. Thus, it has been an interesting research field of life sciences, chemistry and clinical medicine. In this dissertation, on the basis of the previous research, the fluorescence spectroscopy combined with UV-visible absorption spectroscopy was used to investigate the interactions of PCB153and PCB180with HSA in physiological conditions. Furthermore, we make clear the binding mode between PCB153and PCB180with HSA by means of molecular docking and molecular dynamic simulation, which provide strong proofs for the traits of pharmacokinetics and molecular structure. This dissertation contains three parts:Chapterl:The structures, functions and traits of proteins and PCBs were briefly introduced and summarized the detriments of PCBs in environment and body. The main binding sites of HSA and interaction of PCBs with protein were reviewed. The idea of the study was proposed.Chapter2:Under the imitated physiological condition, the interactions of PCB153with Human serum albumin (HSA) were investigated by fluorescence spectrum and absorption spectroscopy. It was shown that this compound had a quite strong ability to quench the fluorescence launching from Endogenous fluorescent (TRP and TYR) in HSA. The quenching belonged to static fluorescence quenching. The thermodynamic analysis which calculated binding constants and binding sites proved that the binding behavior between PCB153and HSA is mainly governed by hydrophobic force; furthermore, as evidenced by site marker displacement experiments using two probe compounds, phenylbutazone (PHE) and ibuprofen (IB), it revealed that PCB153binds exactly at the subdomain IIIA (site II) of HSA as same as ibuprofen (IB) not phenylbutazone (PHE). Molecular docking was utilized to characterize the models of HSA-PCB153complexes, which revealed that the PCB153can bind in a large hydrophobic activity of subdomain IIIA, mainly by the hydrophobic interaction but also by electrostatic interactions.Chapter3:Under the imitated physiological condition, the interactions of PCB180with Human serum albumin (HSA) were investigated by fluorescence spectrum and absorption spectroscopy combining with molecular docking and molecular dynamic simulation. It was shown that this compound had a quite strong ability to bind HSA in sitell by means of Competitive substitution reaction.