. Although site-specific conjugation strategies have been developed that improve the yield and specificity of the conjugation site5,6, issues remain with the cost and intrinsic heterogeneity of the PEG itself7.

maximal hydrodynamic radius to shield its protein payload, we first excluded hydrophobic amino acids (F, I, L, M, V, W and Y), which typically contribute to compact structures and/or protein aggregation.

Renally cleared PEGylated proteins or their metabolites may accumu-late in the kidney, causing formation of PEG hydrates that interfere with normal glomerular filtration. In addition, animals and humans can be induced to make antibodies to PEG9,10