PEGylation was first described in the 1970s by Davies and Abuchowsky. Poly(ethylene glycol), PEG for short, is a highly investigated polymer for the covalent modification of biological macromolecules for pharmaceutical and biotechnical applications. Relevant physicochemical and biological properties of PEG and PEG-conjugates can significantly improve the pharmacokinetic and pharmacodynamic behavior. As a bio-compatible material, this PEG-protein conjugates are nontoxic, non-immunogenic, non-antigenic, highly soluble in water and approved by FDA for human usage. Compared with the original “naked” protein therapeutics, the PEG-drug conjugates have several improvements:
1 Reducing kidney excretion and prolonging in vivo half-life for increased size;
2 Reducing degradation by protecting fragile amino acid residues and masking critical sites sensitive to metabolic enzymes;
3 Masking specific critical sites or surface to reduce immunogenicity of protein drugs;
4 Increasing the solubility of protein therapeutics in physiological fluids;
5 Reduction of the opsonization of liposomes, microparticles or protein adhesion of surfaces coated with PEG, to increase the biocompatibility;
6 Reduction of protein aggregation.
Due to these favorable properties, PEGylation now plays an important role in drug delivery, to enhance the potentials of peptides and proteins as therapeutic agents. Creative Proteomics can help you to characterize the site-specific PEGylation, with two analytical techniques: Edman Degradation and LC-MS based analytical method. The sequence, and modified amino acid residues can be determined with high confidence.
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