Modified PEGylation Based Half-Life Extension Service
For Research Use Only. Not for Clinical Use.
Overview of Modified PEGylation based Half-Life Extension
Modification of protein drugs by covalent attachment of polyethylene glycol (PEG) can improve physical and thermal stabilities, protect against degradation by enzymes, enhance solubility, reduce renal clearance, prolong circulating half-life, and, in some cases, reduce the immunogenicity of the polypeptide. The circulatory half-life of a parenterally administered therapeutic protein may be extended significantly by the covalent attachment of one or more chains of PEG. PEGylation of proteins represents a significant manufacturing challenge in that coupling reaction between chemically activated PEG and free amino groups, even after extensive optimization, commonly results in multiple PEGylated isoforms with nonuniform chemical and pharmaceutical properties. Over the decades, there have been efforts to further develop PEG conjugated therapeutics by modifying and conjugating PEG to other moieties. Conjugating PEG to another molecule is a relatively new approach.
Fig.1 Workflow of phage display constructionand screening (Díez et al. 2015)
Glyco-PEGylation Based Half-Life Extension Service
Glyco-PEGylation based half-life extension is a novel approach for site-directed enzymatic attachment of large PEG groups to the recombinant therapeutic proteins G-CSF, IFN-α2b, and GM-CSF. Selective addition of sialic acid-PEG to O-linked GalNAc on a protein provides a novel, highly site-selective mechanism for PEGylation, enabling the manufacture of long-acting protein drugs with greater structural homogeneity as compared with PEGylated proteins prepared by conventional chemical methods.
Fig. 2. Depiction of GlycoPEGylation strategies. (DeFrees, 2006)
Biotinylated PEG Based Half-Life Extension Service
Previous research on intermolecular interactions of avidin and PEGylated biotin demonstrates that a PEG chain can alter not only the affinity but also the stoichiometry of the avidin-biotin complex system. A modified version of PEG was developed by conjugating PEG to streptavidin. It has enormous potential as a pharmacokinetics enhancer for protein and peptide therapeutics. Based on this, a modified version of PEG was developed by conjugating PEG to streptavidin. It has enormous potential as a pharmacokinetics enhancer for protein and peptide therapeutics. Biotinylated PEG was applied for surface modification of carbon apatite nanoparticles (Co3AP-NP) carrying Gemcitabine. Biotinylated PEG was found to enhance the residence time of the drugs in blood circulation in mice models. In another study, researchers used bovine carboxypeptidase A (CPA) as a target enzyme and successfully prepared a few different formulations of avidin-biotin-PEG-CPA complex using different molecular weight PEG combined with avidin-biotin. In vitro results showed a half-life of 3-4 days depending on PEG chain length, indicating a good improvement in circulation residence time. Therefore, it has enormous potential as a pharmacokinetics enhancer for protein and peptide therapeutics.
Custom Services of Modified PEGylation Based Half-Life Extension
Modifying and conjugating PEG to other moieties has been drawing more and more attention in half-life extension. These methods promise to remedy some of the shortcomings of PEGylation and gradually become a new alternative to PEGylation. As a biotechnology company that never stops pursuing the frontiers, Creative Biolabs has also thrown a lot of manpower, materials, and financial resource into modified PEGylation-based half-life extension research and thus accumulated extensive experiences. With rich experience and years of practice, we can provide our clients with quality-guaranteed modified PEGylation-based half-life extension services to help accelerate our customers' research.
If you are interested in modified PEGylation-based half-life extension services, or you have any questions about our services, please don't hesitate to contact us for more information.
References
- Tan, H.; et al. Recent Advances in Half-life Extension Strategies for Therapeutic Peptides and Proteins. Curr Pharm Des. 2018, 24(41): 4932-4946.
- DeFrees, S.; et al. GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli. Glycobiology. 2006, 16(9): 833-43.
Related Services:
Please submit a detailed description of your project. Our industry-leading scientists will review the information provided as soon as possible. You can also send emails directly to for inquiries.
For Research Use Only. Not for Clinical Use.