Glossary
PEGylation
PEGylation links polyethylene glycol to a peptide so the kidneys clear it more slowly. What it changes for half-life, for mass and for reading the vial label.
PEGylation means covalently attaching one or several polyethylene glycol chains to a peptide, typically at the N-terminal amine, at a lysine side-chain amine, or at a cysteine thiol introduced for the purpose. The polymer drags along a sizeable shell of structured water, so a 3 kDa peptide bearing a 5 kDa PEG behaves in solution like a protein several times its real molecular weight. This lifts it above the kidney’s glomerular filtration cut-off and physically screens cleavage sites from proteases.
Effect on half-life
In practice the result is a longer half-life in the circulation. PEG-MGF is the well-known catalogue example: rodent studies report that the unmodified mechano-growth-factor fragment is cleared within minutes, whereas the PEGylated version remains much longer — which is why the two are used to answer different questions and are not substitutes for each other.
PEGylation also undermines a simple mass assumption. The labelled milligrams of a PEGylated product include the polymer, so each vial holds less peptide than the same nominal mass of unmodified material; molar calculations must be based on the conjugate’s mass, not that of the parent sequence. PEG is also polydisperse, so mass spectra show a spread of peaks instead of a single sharp ion, and purity values on a certificate of analysis need to be interpreted accordingly. See the PEG-MGF overview and why DAC, PEG and acetylation exist.
Related terms
DAC · analog · IGF peptides collection