The Spectroscopy Study On The Interaction Of The Three Drugs And BSA/ct-DNA

As we know, Serum albumin and DNA are biologically active macromolecules with important physiological functions. They have an effect on the transshipment and storage of arious drugs and other small molecules, and they are often used as biological models. So the study of the interactions of small organic molecules in particular drug molecules with serum albumin or DNA is of great importance, such as for understanding its stored state, existence forms, pharmacological functions and the metabolism. And it also provided guidance for the evaluation of drugs efficacy and the development of efficiently novel drugs. This paper has carried on the study about the mechanism between small drug molecules and serum albumin or DNA by spectroscopy. The main contents of this paper are as follows:1. The interactions of the Sim, Gli, SASP and the bovine serum albumin (BSA) were investigated by fluorescence spectrometry and UV-Vis spectroscopy. The quenching constants of system at different temperatures have been calculated to infer the quenching mechanism. The binding force was deduced by calculating the value of△Hθ and△Sθ on the basis of van’t Hoff and other thermodynamic equations. The conformational changes of BSA induced by drugs were monitored by synchronous fluorescence spectroscopy and circular dichroism. The results showed that drugs could strongly quench the intrinsic fluorescence of BSA through a static quenching procedure, and the process also accompanied with a non-radiative transfer of energy. In the quenching,△Hθ<0and△Sθ<0, the drugs binding to BSA depended on hydrogen bonding and van der Waals forces. In the binding, the conformation of BSA was changed by drugs.2. Fluorescence spectroscopy, fluorescence lifetime and three-dimensional fluorescence spectroscopy were used to determine the effect of Ca2+, Fe3+, or Mg2+on the interaction between Gli and BSA. The results showed that in the presence of metal ions, the quenching mechanism for BSA and Gli is still a static procedure. Among the metal ions, decreases BSA-Gli binding constant.△Gθ<0and△Sθ<0, suggesting hydrogen bonding and van der Waals forces were the main binding force. Three-dimensional fluorescence showed that among the metal ions, the fluorescence intensity of two peaks occured further quenched, changed the secondary structure of BSA.3. The complexes of Sim-Ce and Gli-Ce were synthesized. The binding of two complexes to BSA have been investigated by a variety of spectroscopic techniques. The quenching constants, the binding constants, the number of binding sites and the values of thermodynamic parameters were obtained to infer the quenching mechanism and the type of binding force. With the theory of Forster energy transfer the distance was calculated. The probe was used to position. The results showed that two complexes quenched the intrinsic fluorescence of BSA mainly by a static process, but also accompanied by a non-radiative transfer of energy. In the quenching, hydrogen bonding and van der Waals forces were the main binding force. The binding occurred in the Site II of BSA molecular and the distance was1.70nm and1.75nm for Sim-Ce and Gli-Ce to BSA. 4. Hill’s coefficients were used to analysis of synergy Sim, Gli on BSA. Synchronous fluorescence spectroscopy and circular dichroism were used to determine the effect of combination therapy on the secondary structure and conformation of BSA. The results showed that KA(BSA-Sim)>KA(BSA-Gli-Sim),KA(BSA-Gli)>KA(BSA-Sim-Gli), Hill’s coefficients of the ternary systems were less than1. From the synchronous fluorescence, it was found that the synergy between Sim and Gli change the conformation of BSA. According to the CD, a-helix changes changed when two drugs coexistence. It showed that a negative cooperativity is found when Sim and Gli simultaneously bound to BSA. The negative cooperativity made the concentration of free drugs at targets would increase and improved the efficacy of the drugs. Therefore, the two drugs in combination should be strictly controlled doses, which provided a theoretical guidance for clinical drug.5. The interaction of the Sim, Gli, SASP and ctDNA were investigated by fluorescence spectroscopy, UV-Vis spectroscopy. The effects of Sim, Gli, SASP and ctDNA at different temperatures were discussed. The bonding mechanism was explored by viscosity measurements and salt effect. The results showed that drugs and MB-ctDNA was a static enhancement process, there was a strong interaction between the drugs and ctDNA. Hydrogen bonding and van der Waals forces were the main binding force. The mode of action was intercalation.