Feng Feiling, Li Tiehua, Liang Yingchao, Gao Wei, Yang Liang
Department of Biliary Tract Surgery I, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Department of Radiotherapy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126392. doi: 10.1016/j.ijbiomac.2023.126392. Epub 2023 Aug 16.
Exploring the interaction of small molecules with therapeutic proteins can provide useful information about development of ligand-protein complexes as synergistically therapeutic platforms. In this study, the interaction of sinensetin with human interferon gamma (IFNγ) was evaluated experimentally and theoretically. Also, the synergistic effects of IFNγ- sinensetin complex on the inhibition of hepatocellular carcinoma HepG2 cell proliferation were assessed by cell viability and quantitative real time PCR assays. It was realized that sinensetin interacts with IFNγ through a static quenching mechanism and hydrophobic forces mediated by presence of Lys55 and Lys58 amino acid residues in the binding site were the main contributing forces in the spontaneous formation of IFNγ-sinensetin complex. Also, the interaction of sinensetin with IFNγ did not induce a significant change in the secondary and tertiary structure of the protein. Cellular assays revealed a synergistic effect of sinensetin on IFNγ -triggered anticancer action in HepG2 cells through overexpression of caspase-3 mRNA and protein. In conclusion, this study may hold great promise for the development of potential ligand- protein complexes for therapeutic purposes.
探索小分子与治疗性蛋白质之间的相互作用可为配体 - 蛋白质复合物作为协同治疗平台的开发提供有用信息。在本研究中，通过实验和理论评估了橙皮素与人干扰素γ（IFNγ）之间的相互作用。此外，通过细胞活力和定量实时PCR分析评估了IFNγ - 橙皮素复合物对肝癌HepG2细胞增殖抑制的协同作用。结果发现，橙皮素通过静态猝灭机制与IFNγ相互作用，结合位点中存在的Lys55和Lys58氨基酸残基介导的疏水力是IFNγ - 橙皮素复合物自发形成的主要作用力。此外，橙皮素与IFNγ的相互作用并未引起蛋白质二级和三级结构的显著变化。细胞分析显示，橙皮素通过caspase - 3 mRNA和蛋白质的过表达对HepG2细胞中IFNγ触发的抗癌作用具有协同作用。总之，本研究可能为开发用于治疗目的的潜在配体 - 蛋白质复合物带来巨大希望。
