Abstract by Seth Earl
Chemistry and Biochemistry
The Effects of PEGylation on Hydrogen Bonding
The conjugation of peptide chains with poly-ethylene glycol (PEG) has been used for several years to increase the pharmacokinetics of protein based drugs. The addition of PEG to a peptide chain increases the serum half life of the peptide chain and allows the peptide to last longer by blocking renal clearance and enzymatic proteolysis of the peptide chain. Data from the Price lab has shown that PEGylation using short PEG chains increases conformational stability when attached to a favorable conjugation sites. The research that we are doing relates to PEG location and how it affects conformational stability of proteins that participate in hydrogen bonding. Preliminary data shows that PEGylation of asparagine 26 (Asn) increases the overall conformational stability of the protein. We tested whether PEG stabilizes the hydrogen bond by changing tryptophan 11 (Trp) to phenylalanine (Phe). Phe is less aromatic than Trp, and mutation should result in decreased conformational stability due to the weakening of the hydrogen bond.