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Pegylation and Glycosylation

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Formation factors. Pegylation, another strategy to modify the biologic structure. And that refers to the covalent bonding of polyethylene glycol to the therapeutic proteins.
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And with pegylation, it reduces immunogenicity by shielding the antigenic or the immunogenic epitopes, the site of the immunogenicity. PEG also acts as a shield to protect the protein from proteolytic enzymes. And it also reduces aggregation by way of increasing solubility because of the addition of the hydrophilic moiety. Polyethylene glycol is hydrophilic. And pegylation has an advantage because the PEG of the polyethylene glycol is already an approved a drug for human use. And this slide shows a list of pegylated product and I’ll just show you two examples here. Neulasta. Neulasta is a granulocyte colony-stimulating factor used for cancer chemotherapy to reduce neutropenia. Pegasys, this drug or this biologic, you can even tell, is PEGylated by the name, PEG.
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And it’s used for chronic hepatitis C it’s pegylated interferon product. By the way, in the last section of this mini-series, we will talk about or discuss more products. Now there is a paradox for structural modification. We know chemical structure modification is intended to reduce immunogenicity.
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But it may also render the therapeutic protein less active or less potent, because after modification it is no longer the same original protein molecule. And the extension of half-life increases the time length of exposure to the immune system which can potentially increase immunogenic response. Increase the molecular size by covalent attachment glycans of poly ethylene glycol could also raise immunogenicity simply by increasing the size of the molecule. So as you can see here, there are multiple factors that inter-play with each other to yield a net effect.

PEGylation and glycosylation are utilized to modify protein by forming protein-polymer conjugates with different assembled structure and enzyme activity. The coupling via click chemistry induce further self-assembly of conjugates into spherical nanoparticles with well dispersion stability, a favorable formulation attribute

Pegylation is the process of covalent attachment of polyethylene glycol (PEG) polymer chains to a protein. It works by shielding the antigenic and immunogenic epitopes of the protein to reduce immunogenicity. The PEG polymer also protects the protein from proteolytic enzymes. Last but not least, the hydrophilic attachment reduces aggregation and increases solubility of the protein.

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Pharmacotherapy: Understanding Biotechnology Products

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