Abstract by Brian Harris
Chemistry and Biochemistry
The Impact of PEGylation on Salt Bridge Interactions
PEGylation of protein side chains has been used for several decades to enhance the pharmacokinetic properties of certain protein drugs. PEGylation is the process of attaching a polyethylene glycol (PEG) to a specific site on a protein to increase overall stabilization. While PEGylation has proven to increase stabilization at times, we do not yet understand the full extent of circumstances in which PEG can be used to strengthen proteins.
Our research was designed to increase understanding of how PEGylation affects the stability of salt bridge interactions in proteins. We have found that as the strength of the salt bridge decreases, the potential to have PEG-based stabilization increases. By measuring the dihedral angles between salt bridge residues, we were able to predict the strength of salt bridges in proteins, which allowed us to discern ideal locations to attach PEG. Using this information we discovered that using PEG to increase stabilization of weak salt bridge interactions increases the overall stability of the protein.