Spectroscopic Studied On The Interaction Between Protein With Small Drug And Analogs Molecules

The interactions between drugs and proteins have been widely studied in the field of bioscience, clinical medicine, pharmaceutics and so on. Proteins pl ay a significant function in sustaining life, while drugs play a important role in the health of people. Human serum albumin (HSA) and Bovine Serum Alb umin (BSA) is one of the endogenous fluorescent substances; Ovabumin (OV A) is a phosphorylated and glycosylated globular protein.Derivatives of fluoraz one (9H-pyrrolo[1,2-a]indol-9-one)(3a) show a broad spectrum of biological a ctivities such as antidiabetic and anticancer; Bifendate is synthetic novelanti-he patitis drugs, which can anti-hepatitis virus actions and hepatoprotectiveactiviti es; Caffeine, theophylline, and diprophylline, which have important pharmacolo gy function, are purine alkaloids with similar structure.Caffeine has been gene rally believed to abolish free radical and support a healthy heart, theophylline and diprophylline are used for the treatment of bronchial asthma andcoronary insufficiency. Therefore, the pharmacokinetics and pharmacodynamics of drugs in the human system are greatly affected by their interactions, which have a significant meaning to the designing and exploiting of new drugs.In this thesis, the interaction between drugs and proteins were investigat ed by the aid of intrinsic fluorescence, synchronous fluorescence, three-dimens ional fluorescence, ultraviolet-vis absorbance, resonance light-scattering spectra and molecular docking techniques. There are four sections:Sectfon1:In this chapter, the pharmacological activity and application of drugs and proteins were briefly presented; the research methods and contents of bingding of drugs to proteins were mainly introduced.Sectfon2:The interactions of human serum albumin with series of Fluorazone isomeric derivatives have been studied by spectrophotometric methods. Results showed that the intrinsic fluorescence of human serum albumin is quenched by the derivatives with a static quenching procedure. The binding constants are obtained at T=27、49℃. The thermodynamics parameters (△H,△S,△G) indicate the major force type. Meanwhile, the binding distance r was obtained between donor and acceptor by Foster energy transfer theory. The results of synchronous fluorescence, three-dimensional fluorescence spectra, indicated a conformational change of human serum albumin with addition of Fluorazone isomeric derivatives.Section3:The interaction between bovine serum albumin and analogs of Biphenyldicarboxylate was investigated. It was found that that the nature of the quenching was of static type. The binding constants were determined at T=22、32.42℃, and the process of binding was a spontaneous molecular interaction procedure. The thermodynamics parameters (AH, AS, AG) indicate the major force type. The distance between donor and acceptors was obtained according to Forster’s theory. The influence of analogs on the conformation of bovine serum albumin were analyzed by the aid of synchronous fluorescence and three-dimensional fluorescence spectra. Using resonance light-scattering spectra, the size of analogs of Biphenyldicarboxylate-BSA particles were compared.Section4:The interaction between Ovalbumin (OVA) and caffeine, theophyll-ine and diprophylline was investigated. Results showed that the formation of complexes gave rise to the fluorescence quenching of OVA by caffeine, theophylline, and diprophylline. Static quenching was confirmed to results in the fluorescence quenching. The binding site number n, apparent binding constant KA and corresponding thermodynamic parameters were measured at T=14、24℃. According to Forster’s theory, the distance between donor and acceptors was no more than7nm. The influence of anafogs on the conformation of Ovalbumin were analyzed by the aid of synchronous fluorescence and three-dimensional fluorescence spectra. What’s more, The influence of molecular structure on the binding aspects was reported. By the aid of resonance light-scattering spectra, the size of alkaloids-OVA particles were compared.