Bioinspired protein microparticles fabrication by peptide mediated disulfide interchange

In this article, we report an innovative green chemistry approach for the fabrication of protein microparticles based on peptide mediated disulfide interchange reactions. The concept is based on using a redox reactive peptide, glutathione, as a natural crosslink reagent triggering the formation of intermolecular disulfide bonds between adjacent protein molecules leading to the assembly of protein molecules within a CaCO3 template into a microparticle structure. The CaCO3 template is highly biocompatible and is completely removed by simply adjusting the solution to pH 5.0, leaving behind the pure protein microparticles. Moreover, the GSH is only involved in the intermediate step without being incorporated into the resulting protein microparticles, therefore producing protein microparticles composed of purely protein molecules. This technology provides a simple and robust method to fabricate protein microparticles under physiological aqueous conditions, and more importantly avoiding the extensive use of synthetic chemical crosslinking reagents. We have further demonstrated that this method is versatile to fabricate microparticles with various proteins such as BSA, enzymes and antibodies. The biological functions such as catalytic properties and affinity interactions of the resulting protein microparticles are highly conserved which demonstrate the potential applications of the protein microparticles in the area of biocatalysis, bioseparation and targeted drug delivery