Meng Tong, Wang Zhiguo, Zhang Hao, Zhao Zhen, Huang Wanlin, Xu Liucheng, Liu Min, Li Jun, Yan Hui
School of Pharmaceutical Sciences, Liaocheng University, Liaocheng 252059, China.
Institute of Ageing Research, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Molecules. 2024 Feb 22;29(5):956. doi: 10.3390/molecules29050956.
Piceatannol (PIC) and epigallocatechin gallate (EGCG) are polyphenolic compounds with applications in the treatment of various diseases such as cancer, but their stability is poor. β-lactoglobulin (β-LG) is a natural carrier that provides a protective effect to small molecule compounds and thus improves their stability. To elucidate the mechanism of action of EGCG, PIC, and palmitate (PLM) in binding to β-LG individually and jointly, this study applied molecular docking and molecular dynamics simulations combined with in-depth analyses including noncovalent interaction (NCI) and binding free energy to investigate the binding characteristics between β-LG and compounds of PIC, EGCG, and PLM. Simulations on the binary complexes of β-LG + PIC, β-LG + EGCG, and β-LG + PLM and ternary complexes of (β-LG + PLM) + PIC, (β-LG + PLM) + EGCG, β-LG + PIC) + EGCG, and (β-LG + EGCG) + PIC were performed for comparison and characterizing the interactions between binding compounds. The results demonstrated that the co-bound PIC and EGCG showed non-beneficial effects on each other. However, the centrally located PLM was revealed to be able to adjust the binding conformation of PIC, which led to the increase in binding affinity with β-LG, thus showing a synergistic effect on the co-bound PIC. The current study of β-LG co-encapsulated PLM and PIC provides a theoretical basis and research suggestions for improving the stability of polyphenols.
白皮杉醇（PIC）和表没食子儿茶素没食子酸酯（EGCG）是具有多种疾病治疗应用（如癌症治疗）的多酚类化合物，但它们的稳定性较差。β-乳球蛋白（β-LG）是一种天然载体，可为小分子化合物提供保护作用，从而提高其稳定性。为阐明EGCG、PIC和棕榈酸酯（PLM）单独及联合与β-LG结合的作用机制，本研究应用分子对接和分子动力学模拟，并结合包括非共价相互作用（NCI）和结合自由能在内的深入分析，来研究β-LG与PIC、EGCG和PLM化合物之间的结合特性。对β-LG + PIC、β-LG + EGCG和β-LG + PLM的二元复合物以及（β-LG + PLM）+ PIC、（β-LG + PLM）+ EGCG、β-LG + PIC）+ EGCG和（β-LG + EGCG）+ PIC的三元复合物进行模拟，以比较和表征结合化合物之间的相互作用。结果表明，共结合的PIC和EGCG对彼此显示出不利影响。然而，位于中心位置的PLM能够调节PIC的结合构象，这导致其与β-LG的结合亲和力增加，从而对共结合的PIC显示出协同作用。目前对β-LG共包封PLM和PIC的研究为提高多酚稳定性提供了理论依据和研究建议。
