Definition
PEGylation attaches one or more polyethylene glycol (PEG) chains to a peptide or protein, usually through a lysine amine, the N-terminus or an engineered cysteine. PEG is hydrophilic and flexible, so it enlarges the molecule's hydrodynamic size, reduces renal filtration and shields the backbone from proteases. In pharmacokinetic studies, PEGylated analogues generally show longer half-lives than their parent sequences. The trade-offs include reduced receptor affinity from steric hindrance, heterogeneity when PEG attaches at several sites, and reports of anti-PEG antibodies in some studies. Because PEG polymers are polydisperse, PEGylated peptides give broad mass spectra rather than a single sharp peak, which complicates identity testing.