Characterization Of Interaction Of Biological Macromolecules With Tinibs

In this article, interaction of gefitinib with DNA and interactions of gefitinib, lapatiniband sunitinib with BSA have been studied through a variety of spectroscopy combined with molecular modeling methods to understand the binding mode and binding force, as well as the effects of drugs on the structure of biological macromolecules.The binding mode of gefitinib with calf thymus DNA(ct-DNA) at physiological p H was studied employing UV absorption, fluorescence and viscosity measurement. The experimental results revealed that gefitinib preferred to bind to the minor groove of ct-DNA with the binding constent(Kb) of 6.44×103 mol/L at 298 K. Base on the signs and magnitudes of the enthalpy change and entropy change in the binding process and the results of molecular docking, it can be conclude that the main interaction forces between gefitinib and ct-DNA in the binding process were vander Waals force and hydrogen bonding interaction. The results of CD experiments revealed that gefitinib did not disturb native B-conformation of ct-DNA. And, the change was close relation with the structure of B-DNA fragments, indicating that the flexibility of gefitinib molecule also plays an important role in the formation of the stable gefitinib-ct-DNA complex.Synchronous fluorescence spectroscopy, fluorescence spectroscopy, circular dichroism and molecular simulation were used to study the interaction of gefitinib, lapatinib and sunitinib with BSA. The experimental results showed that the fluorescence quenching of the BSA at 338 nm by three tinibs drugs. And the number of binding sites(n) between three tinibs drugs and BSA was approximately equal to 1. The enthalpy change and entropy change indicated that the main interaction forces between three tinibs drugs and ct-DNA in the binding process were vander Waals force and hydrogen bonding interaction. The results of Circular dichroism and synchronous fluorescence spectroscopy suggested that three tinibs drugs did not disturb the secondary structure of BSA. Moreover, fluorescent competition suggested that gefitinib and sunitinib compete with phenylbutazone on site I of BSA, lapatinib competes with lbuprofen on site II of BSA; At last, molecular docking was used to explain the binding process of drug and BSA in micro-level respect.