title: How PEGylation influences protein conformational stability.
abstract: PEGylation is an important strategy for enhancing the pharmacokinetic properties of protein therapeutics. The development of chemoselective side-chain modification reactions has enabled researchers to PEGylate proteins with high selectivity at defined locations. However, aside from avoiding active sites and binding interfaces, there are few guidelines for the selection of optimal PEGylation sites. Because conformational stability is intimately related to the ability of a protein to avoid proteolysis, aggregation, and immune responses, it is possible that PEGylating a protein at sites where PEG enhances conformational stability will result in PEG-protein conjugates with enhanced pharmacokinetic properties. However, the impact of PEGylation on protein conformational stability is incompletely understood. This review describes recent advances toward understanding the impact of PEGylation on protein conformational stability, along with the development of structure-based guidelines for selecting stabilizing PEGylation sites.
authors: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, United States.
authors: Paul B
authors: PB
authors: Lawrence
authors: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, United States.
authors: Joshua L
authors: JL
authors: Price
mesh_terms: D010599:Pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D011092:Polyethylene Glycols