Fu Linna, Liu Guangbin, Zhao Dongxin, Yuan Libo, Lu Kui
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450001, China; School of Chemical Engineering and Food Science, Zhengzhou University of Technology, Zhengzhou 450044, China.
Chemical College, Zhengzhou University, Zhengzhou 450001, China.
Spectrochim Acta A Mol Biomol Spectrosc. 2021 Jul 5;255:119673. doi: 10.1016/j.saa.2021.119673. Epub 2021 Mar 9.
Peptide drugs, which are mainly used for the treatment of AIDS, myeloma, and breast cancer, have evolved rapidly owing to their high efficacy and low side effects. The interaction mechanisms of two peptide drugs with two biological macromolecules (protein and DNA), which are of great significance in disease prevention and drug design, were investigated using molecular docking, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, UV-visible spectroscopy and viscosity measurements. The interaction between a series of common drugs and ovalbumin (OVA) was simulated by molecular docking, and two peptide drugs with the highest energy values, namely atazanavir and carfilzomib, were selected; the binding energy values of these drugs with OVA were -59.20 and -55.93 kcal/mol, respectively. The K values of the interaction of the two drugs with OVA/DNA were in the range of 10-10 M, and the binding affinity of the drugs was stronger with OVA than with DNA. Hydrogen bonds and van der Waals forces were very important for the binding between drugs and OVA through molecular docking studies, and it was consistent with experimental results (ΔH < 0, ΔH < 0). The synchronous fluorescence spectrum showed that the interaction caused a change to the original structure of OVA, and atazanavir had a greater effect on OVA than carfilzomib. CD spectrum analysis also demonstrated that the conformation of OVA changed slightly. The interaction between atazanavir and DNA was mainly driven by hydrophobic forces (ΔH > 0 and ΔH > 0), whereas the major interaction forces involved in the binding of carfilzomib with DNA were hydrogen bonds and van der Waals forces. DNA melting studies, UV-visible spectroscopy, CD spectroscopy and viscosity measurements established that the interaction between the drugs and DNA was groove binding.
肽类药物主要用于治疗艾滋病、骨髓瘤和乳腺癌，因其高效低毒而发展迅速。利用分子对接、荧光光谱、圆二色（CD）光谱、紫外可见光谱和粘度测量等方法，研究了两种肽类药物与两种生物大分子（蛋白质和DNA）的相互作用机制，这在疾病预防和药物设计中具有重要意义。通过分子对接模拟了一系列常用药物与卵清蛋白（OVA）之间的相互作用，选择了能量值最高的两种肽类药物，即阿扎那韦和卡非佐米；这些药物与OVA的结合能值分别为-59.20和-55.93千卡/摩尔。两种药物与OVA/DNA相互作用的K值在10-10 M范围内，药物与OVA的结合亲和力强于与DNA的结合亲和力。通过分子对接研究发现，氢键和范德华力对药物与OVA的结合非常重要，这与实验结果一致（ΔH < 0，ΔH < 0）。同步荧光光谱表明，这种相互作用导致OVA的原始结构发生变化，阿扎那韦对OVA的影响大于卡非佐米。CD光谱分析也表明OVA的构象略有变化。阿扎那韦与DNA之间的相互作用主要由疏水力驱动（ΔH > 0且ΔH > 0），而卡非佐米与DNA结合涉及的主要相互作用力是氢键和范德华力。DNA熔解研究、紫外可见光谱、CD光谱和粘度测量表明，药物与DNA之间的相互作用是沟槽结合。
