PEGylation
The process of attaching polyethylene glycol (PEG) polymer chains to a peptide or protein to extend its half-life in the body. PEGylation increases molecular size (reducing kidney filtration) and shields the peptide from enzymatic degradation. Palopegteriparatide is an example of a PEGylated peptide drug.
Technical Context
PEG chains range from 5 to 40+ kDa and increase the molecule's hydrodynamic radius, reducing glomerular filtration by the kidneys and creating a hydrophilic shield against proteolytic enzymes. The degree and site of PEGylation must be carefully optimised — over-PEGylation can sterically hinder receptor binding and reduce biological activity. Palopegteriparatide is a PEGylated PTH that provides sustained parathyroid hormone activity. Somapacitan uses a different half-life extension approach (albumin binding via a C-18 fatty acid) rather than PEGylation. Concerns about PEG immunogenicity (anti-PEG antibodies) and PEG accumulation in tissues have led to exploration of alternative polymer conjugation strategies.