Abstract by Nathaniel Brown
Chemistry and Biochemistry
Non-specific conjugation of polyethylene glycol (PEG) has long been used to improve protein drug effectiveness by increasing proteolytic resistance and thermodynamic stability of peptides. However, non-specific protein mutagenesis may alter protein function and effectiveness. To improve on this technique, our lab has done extensive research on site-specific PEGylation that both inhibits proteolysis while maintaining protein function. Another method of protein stabilization, hydrocarbon stapling, physically restricts protein conformation, thereby causing the protein to maintain an active form. By combining site-specific PEGylation and previous stapling methods, we have created a novel PEG-stapling method. This method may increase protein stability by combining the stability due to a restricted protein conformation found in stapled peptides with the stabilizing effects due to site-specific PEGylation.