Characterization Of Interaction Of Nucleoside Drugs With Human Serum Albumin And Its Application

Protein is essential to life. Serum albumin, the most abundant protein in blood plasma, can storage and transport many substances, including endogenous substances and exogenous substances. As a transport carrier in vivo, the analysis and determination of serum albumin is indicative of diagnosis and therapy in clinic study for a long time. Fluorescence technic is a broad-used method to study the interaction of drugs with protein since it has high rapidity and sensitivity. Based on the previous study, the interaction of nucleoside drugs with human serum albumin was investigated by using many experiment methods including spectra and molecular modeling, and the experiments were carried out under simulative conditions, these nucleoside drugs included 2-(9H-purin-6-ylamino)-4-(methylthio) butanoic acid(PYMBA), 8-Bromoadenosine, 2′-deoxyuridine and 5-Methyluridine. six chapters was contained in this dissertation.Chapter 1: The structures and functions of protein; the functions and bioactivities of nucleoside drugs; and the research of interaction between drugs and protein.Chapter 2: The interaction of PYMBA with human serum albumin was first studied by using fluorescence spectra, UV spectra and molecular modeling; The experiment results indicated that PYMBA binded to serum albumin mainly by hydrophobic force, as well as hydrogen bonds; Molecular modeling results indicated that PYMBA binded to the subdomain IIA of human serum albumin.Chapter 3: Fluorescence spectra was used under simulative conditions to study the binding of 8-Bromoadenosine with human serum albumin; 8-Bromoadenosine could bind to human serum albumin to form a new compound by hydrophobic force, thus quenched the fluorescence of human serum albumin, the mechanism was static quenching; The binding distance between 8-Bromoadenosine and human serum albumin was 3.66 nm; A new method to determine the total proteins in biology samples was founded with 8-Bromoadenosine as a probe.Chapter 4: The binding of 2′-deoxyuridine to HSA was studied by spectroscopic method and molecular modeling; The binding constant between 2′-deoxyuridine and HSA was 3.460×104 L/mol, which indicated that there was a strong binding between them; The binding forces between them was hydrophobic force and hydrogen bonds; Based on the interaction, the determination of proteins in biological samples were carried out with 2′-deoxyuridine as a molecular probe by synchronous fluorescence technique.Chapter 5: Many methods were used to characterize the interaction of 5-Methyluridine and HSA,the quenching constants was calculated according to Stern-Volmer equation, and Lineweaver-Burk equation was used to calculate the binding constants; The binding distance between 5-Methyluridine and HSA was 3.55 nm; Based on the interaction, a method was established to determine the total proteins in biology samples, which results were satisfactory.Chapter 6: summarizes and prospects.