Peptide disulfide RKCGCFF facilitates oxidative protein refolding by mimicking protein disulfide isomerase

• Hydrophobic and positively charged residues were incorporated into CGC disulfide.
• The new oxidant RKCGCFF was more similar to PDI in structure and properties.
• RKCGCFF was more effective than RKCGC in facilitating lysozyme refolding.
• RKCGCFF improved refolding yield of lysozyme at a high concentration.

This communication reports a new design of peptide disulfide, RKCGCFF, for facilitating oxidative protein refolding. The new design mimics the properties of protein disulfide isomerase (PDI) by introducing hydrophobic and positively charged patches into the two terminals of disulfide CGC. RKCGCFF was found more effective than the traditional oxidant oxidized glutathione (GSSG) as well as its counterpart, RKCGC, in facilitating the oxidative refolding of lysozyme. More importantly, RKCGCFF could improve lysozyme refolding yield at a high concentration (0.7 mg/mL). The research proved that incorporation of hydrophobic and charged patches into the CGC disulfide made the oxidant more similar to PDI in structure and properties.