Design peptide-based nanoparticles to compete mRNA binding site of human antigen R
Abstract:
Human antigen R (HuR), which is over-expressed in cytoplasm to stabilize mRNA and responsible for gene translation at the event of inflammation, appears to be a potential therapeutic target. In this study, we sought to design peptides with high binding affinity at the mRNA binding site of HuR. We found that JS-1, which is an peptide tethered with a hydrophilic polymer, exhibited higher affinity than quercetin (a small-molecule inhibitor of HuR) using Discovery studio and HotLig modeling systems, and can down-regulate inflammatory molecules production in lipopolysaccharide-activated macrophage. Using an imiquimod-induced psoriasis-like dermatitis model, JS-1 significantly ameliorated erythema, skin thickness and scaling in psoriasis mice as compared to quercetin. This study demonstrated that JS-1 exhibited anti-inflammatory effects via competing the mRNA binding site to inhibit gene expression, suggesting that JS-1 may potentially be a therapeutic agent for the treatment of inflammatory diseases.