SOY PEPTIDES ACTIVATE LDL‐R: IN VITRO EXPERIMENTS AND DOCKING DATA

Abstract

The alpha prime region of the soybean 7S globulin subunit has been associated with a decrease in cholesterol both in in vitro and in vivo studies. One possible mechanism of action could be the binding of the protein or its digested fragments either to the LDL receptor itself or to proteins associated with regulation of LDL receptor sequestering and recycling, resulting in enhanced fusion of the LDL receptor storage vesicles with the cell surface. These regulatory proteins include proprotein convertase subtilisin‐like/kexin type 9 (PCSK9). We found that synthetic peptides from 7S soy globulin such as HKQEKHQGKE, NPDNDE and ENLIKSQSES exerted a statistically significant up‐regulation (+ 43%, +54% and +48% at concentration of 10−5M, respectively: P<0.05) of LDL receptors in Hep G2 cells vs controls. In order to explore the hypothesis that the LDL‐R regulation is due to an interaction of these peptides with the regulatory proteins, as above mentioned, molecular modeling experiments (e.g., protein‐ligand docking) were performed using publicly available x‐ray crystal structures of the LDL receptor, PCSK9. Analysis of potential protein ligand interaction generated from these docking studies identified NPDNDE as potentially having a higher binding affinity to PCSK9 than the other peptides. This is consistent with experimentally generated activity data.