Study on The Interaction of Polyoxypregnane Glycosides From Dregea sinensis With Immune Proteins

Objective Based on chemical structural characteristics, the bioactivity of polyoxypregnane glycosides from Dregea sinensis, and the molecular interaction between compounds and targeted proteins were investigated. Methods The bioactive screening of 191 polyoxypregnane glycosides (>800 u), and the kinetic evaluation on human immune-related proteins was carried out by molecular docking and SPR experiment. Results Seven compounds (6, 18, 23, 30, 78, 79, and 80) and 3 immune-related proteins (IL-2Rα, TLR4, and TNF-α) were selected through virtual screening. Compounds 30 and 78 showed the significant binding tendency with IL-2Rα and TLR4 in SPR experiment, and K_D values with IL-2Rα were 2.41×10^-6 and 2.14×10^-6 mol/L, meanwhile K_D values with TLR4 were 1.96×10^-5 and 5.60×10^-6 mol/L, respectively. The interactions between targeted proteins and compounds were further characterized by discovery studio. The analysis of molecular docking revealed the binding pocket residues for SPR-positive molecules 6, 18, 30, 78, and 80. Conclusion The result indicated these glycosides could bind to targeted proteins through forming hydrogen bonds and Pi-Pi interactions. The study is meaningful for bioactive evaluation of polyoxypregnane glycosides, and provides valuable exploration to the underlying mechanisms of effective compounds with low abundance.