Abstract by Dallin Ashton
Chemistry and Biochemistry
Thermodynamic Effects of Site Specific PEGylation Near Solvent Exposed Nonpolar Residues
The attachment of Polyethylene Glycol onto peptide based pharmaceuticals (PEGylation) has been used for many years to increase the serum half lives of these peptides. Advances in site-selective PEGylation have shown that while some sites result in stabilization, others yield null or destabilizing effects. Previously the choice of PEGylation site has often been a matter of trial and error. Here we show that PEGylation near solvent exposed nonpolar amino acid residues stabilizes variants in the WW domain. By mutating native residues to hydrophobic side chains of various sizes, we show increases in solvent exposed hydrophobic surface area, indicated by various decreases in heat capacity. We then note the correlation in solvent excluded volume of the nonpolar residues to stabilization by PEGylation. These findings suggest a pattern for identifying possible sites in peptides with significant exposed nonpolar residues where selective PEGylation could increase conformational stability.