PEGylation is a process of attaching one or more molecules of polyethylene glycol (PEG) to target biomolecules including peptides, proteins and oligonucleotide. It is a vital modification used in biopharmaceuticals to facilitate the functions of therapeutic proteins and peptides. PEGylation improves pharmacokinetic and pharmacodynamic properties of proteins. PEG has been approved as pharmaceutical excipient for injection by FDA.
PEGylation offers many advantages for biologic drugs:
➢ Highly site-specific modifications
➢ Improved solubility and chemical & physical stability
➢ Prolonging in vivo half-life
➢ Decreasing immunogenicity and toxicity
➢ Increasing the biocompatibility
➢ Reducing proteolytic aggregation
➢ Increasing efficacy and clinical effectiveness in vivo
Site-Specific PEGylation of Therapeutic Proteins, Jonathan K. Dozier, Int. J. Mol. Sci. 2015, 16(10)
Since the first PEGylated drug——"Adagen" was approved by the FDA in 1990, there have been several PEGylated products approved by FDA on the market:
PEGylated Protein Analysis Services at Creative Proteomics:
Technical methods
- HPLC/UPLC-MS, peptide mapping, Edman sequencing, NMR, amino acid analysis, size exclusion chromatography and isoelectric focusing electrophoresis for PEGylated sites and heterogeneity analysis
- Immunoassay and bioassay for immunogenicity analysis
- ELISA assay for pharmacokinetic analysis
Table 1 FDA-approved PEGylated drugs
| Commercial name | Drug name | Company | PEG size (Da) | Indication | Year of approval |
|---|---|---|---|---|---|
| Adagen | Pegadamase | Enzon | Multiple linear 5000 | SCID | 1990 |
| Oncaspar | Pegaspargase | Enzon | Multiple linear 5000 | Leukemia (All, CML) | 1994 |
| PEG-INTRON | Peginterferon-α2b | Schering-Plough | Linear 12,000 | Hepatitis C | 2000 |
| PEGASYS | Peginterferon-α2a | Hoffman-La Roche | Branched 40,000 | Hepatitis C | 2001 |
| Neulasta | Pegfilgrastim | Amgen | Linear 20,000 | Neutropenia | 2002 |
| Somavert | Pegvisomant | Pharmacia & Upjojn | 4-6 linear 5000 | Acromegaly | 2003 |
| Macugen | Pegaptanib | Pfizer | Branched 40,000 | Age-related macular degeneration | 2004 |
| Mircera | mPEG-epoetin-β | Hoffman-La Roche | Linear 30,000 | Anemia associated with chronic renal failure | 2007 |
| Cimzia | Certolizumab pegol | UCB | Branched 40,000 | Reducing signs and symptoms of Crohn's disease | 2008 |
| Puricase 1 /Krystexxa | PEG-uricase | Savient | 10,000 | Gout | 2010 |
- ALL: acute lymphoblastic leukemia; CML: chronic myeloid leukemia; SCID: severe combined immunodeficiency disease.
- **See reference: Current drug research on PEGylation with small molecular agents. Wenjun Li, Progress in Polymer Science, 2013, 38.
Creative Proteomics provides comprehensive analytic methods on PEGylated protein drugs for our customers. Scientists from Creative Proteomics are professional and experienced in PEGylation and provide efficient services that meet the requirements of FDA and ICH guidelines. We also offer various customized services to meet customers need.
