期刊
LUMINESCENCE
卷 37, 期 2, 页码 310-322出版社
WILEY
DOI: 10.1002/bio.4173
关键词
ct DNA-H1 complex; intercalative; molecular dynamics; spectroscopy; viscosity
资金
- Islamic Azad University
- Research Council
This study investigated the interaction between PPF and calf thymus DNA (ct DNA) in the absence or presence of histone H1 using multiple spectroscopic techniques. PPF showed high binding affinity towards ct DNA in binary and ternary systems, with intercalation binding mode suggested by fluorescence quenching data and thermodynamic parameters. MD simulation suggested that PPF as an intercalating agent can distort the DNA structure.
With advances in new drug therapies, it is essential to understand the interactions between drugs and target molecules. In this study, we applied multiple spectroscopic techniques including absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, calorimetric, and molecular dynamics (MD) simulation to study the interaction between 2-Ethyl-5-(4-methylphenyl) pyramido pyrazole ophthalazine trione (PPF) and calf thymus DNA (ct DNA) in the absence or presence of histone H1. PPF exhibits a high binding affinity towards ct DNA in binary and ternary systems. In addition, the result for the binding constant was observed within the range 10(4) M-1 achieved through fluorescence quenching data, while the values for enthalpy and entropy changes for ct DNA-PPF and (ct DNA-H1) PPF complexes were measured to be -72.54 kJ.mol(-1), -161.14 J.mol(-1) K-1, -85.34 kJ.mol(-1), and -19.023 J.mol(-1) K-1, respectively. Furthermore, in accordance with circular dichroism spectra, the inducement of ct DNA structural changes was observed during binding of PPF and H1 in binary and ternary system forms. The essential roles of hydrogen bonding and van der Waals forces throughout the interaction were suggested using thermodynamic parameters. According to the obtained data, the interaction mode of ct DNA-PPF and (ct DNA-H1) PPF complexes was intercalation binding. Suggested by the MD simulation study, the ct DNA-H1 complex caused a reduction in the stability of the DNA structure in the presence or absence of ligand, which demonstrated that PPF as an intercalating agent can further distort the structure. The information achieved from this study will be very helpful in understanding the effects of PPF on the conformational state of ct DNA in the absence or presence of the H1 molecule, which seems to be quite significant for clarifying the mechanisms of action and its pharmacokinetics.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据