The synthesis of [

PEGylation is a proven approach to prolonging the duration of action and enhancing biophysical solubility and stability of peptides. 4-Acetylphenylalanine is a novel amino acid with a ketone side chain that is uniquely reactive in proteins. The ketone functionality can react with an aminooxy functionalized polyethyleneglycol polymer to form a stable oxime adduct of the protein. One concern with using unnatural amino acids, such as 4-acetylphenylalanine, is the possibility of it being cleaved from the peptide and becoming incorporated into endogenous proteins. To determine whether this occurs, an in vitro experiment to assess the cell viability and amino acid incorporation into endogenous proteins using primary male rat hepatocytes in the presence of [