Study On The Interaction Of Drug And Protein Xiaoyan Gao (Analysis Chemistry)

The essential biological macromolecules such as protein, nucleic acid,and enzyme, have been playing many vital roles for all kinds of biological phenomena. Proteins is one of the material base of life,it is the important biological molecules of organism. Exploring the interaction mechanisms of the bio-macromolecules with drugs at the molecular level is of current interest in many research fields such as biology, clinical medicine, biology chemistry, medicinal chemistry and so on. Studing the functionary mechanism, binding sites and bining location between drugs and bio-macromolecule can supply the proof to patients and make sure the security and reasonability. This text mainly contains the following sections.1. Under a simulated physiological condition, the interaction between captopril and human serum albumin was studied in vitro. The experiment data showed that a static quenching mechanism play a main role in the fluorescence quenching process of human serum albumin by captopril and the energy transfer between captopril and human serum albumin has occurred. The thermodynamic parameter elucidated the binding reaction was mainly driven by hydrophobic interaction. From the synchronous fluorescence spectra we can seen that the maximum emission wavelength of tryptophan and tyrosine has no apparent shift, it indicated that no significant change in the conformation of HSA upon addition of captopril under experimental conditions.2. Under the simulated physiologic conditions, the interaction between captopril and pepsin was discussed by fluorescence spectrophotometry and UV/Vis spectrophotometry. The experiment data showed that the fluorescence intensity of pepsin was enhanced by the captopril. There is a single binding site between captopril and pepsin by fluorescence enhancing equation and the binding constants of captopril and pepsin are of 1.26×10~5 (291K), 4.98×10~4 (304K) and 4.01×10~4 (310K) at different temperatures, the binding constants reach 10~4 to 10~5 magnitude, indicating that the combination of the two is stronger. The thermodynamic parameters revealed that the binding is a spontaneous process and hydrogen bond, van der Waals force playing a major role in captopril binding to pepsin. From the synchronous fluorescence spectra we can seen that the maximum emission wavelength of tryptophan and tyrosine has no apparent shift, it indicated that conformation of HSA is not changed with the addition of captopril under experimental conditions.3. We studied the interaction between prulifloxacin (PUFX) and pepsin when the Eu(IIII) exists. Through investigation of the quenching mechanism, binding constants, binding sites, binding mode, binding distance, and conformational changes of pepsin, we researched the influence for the interaction of prulifloxacin with pepsin when the existing of Eu(III). The results showed that adding the Eu(III) not only protects the gastric mucosa , but does not affect the the interaction between the pepsin and PUFX.