Study of the noncovalent interactions of ginsenosides and amyloid-beta-peptide by CSI-MS and molecular docking

摘要

Noncovalent interactions between drugs and proteins play significant roles for drug metabolisms and drug discoveries. Mass spectrometry has been a commonly used method for studying noncovalent interactions. However, the harsh ionization process in electrospray ionization mass spectrometry (ESI-MS) is not conducive to the preservation of noncovalent and unstable biomolecular complexes compared with the cold spray ionization mass spectrometry (CSI-MS). A cold spray ionization providing a stable solvation-ionization at low temperature is milder than ESI, which was more suitable for studying noncovalent drug-protein complexes with exact stoichiometries. In this paper, we apply CSI-MS to explore the interactions of ginsenosides toward amyloid-beta-peptide (A beta) and clarify the therapeutic effect of ginsenosides on Alzheimer's disease (AD) at the molecular level for the first time. The interactions of ginsenosides with A beta were performed by CSI-MS and ESI-MS, respectively. The ginsenosides Rg1 bounded to A beta at the stoichiometries of 1:1 to 5:1 could be characterized by CSI-MS, while dehydration products are more readily available by ESI-MS. The binding force depends on the number of glycosyls and the type of ginsenosides. The relative binding affinities were sorted in order as follows: Rg1 approximate to Re > Rd approximate to Rg2 > Rh2, protopanaxatriol by competition experiments, which were supported by molecular docking experiment. CSI-MS is expected to be a more appropriate approach to determine the weak but specific interactions of proteins with other natural products especially polyhydroxy compounds.