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Covalent attachment
of the hydrophilic polymer, polyethylene glycol (PEG), to complex molecules,
especially proteins, has found important applications in drug development.
Pegylation, the attachment of PEG polymers to therapeutic proteins, may
offer the healthcare industry solutions to common protein drug delivery
problems such as poor solubility and stability, proteolytic degradation,
short pharmacokinetic half-life due to clearance by renal filtration and
the reticuloendothelial system (RES), and immunogenicity.
The primary chemical attachment point of PEG polymers has been to functional
groups on a protein’s amino acid sequence. However, this is often
problematic because the PEG polymer either interferes with access to the
protein’s active site or alters the conformation of the active site,
leading to diminished activity of the protein drug.
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Neose’s GlycoPEGylation technology offers a direct and significant application to overcome the pitfalls of traditional pegylation of protein drugs. By uniquely linking PEG polymers to sugar chains that are far removed from the protein’s active site, GlycoPEGylation helps preserve the bioactivity of the drug and extends its half-life.
| GlycoPegylation™
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Neose has developed GlycoPEGylation to conjugate different molecular weight PEG molecules to donor sugars, such as CMP-sialic acid, and then uses glycosyltransferases to link the conjugated sialic acid to the terminating “branches” of the sugar chains on glycoproteins. The multiple attachment sites for sialic acid to sugar chains, along with the ability to utilize PEG polymers of different molecular weight, affords the opportunity to tailor the pegylation of proteins to optimize the pharmacokinetic properties of protein drugs. The same process has proven effective when conjugating PEG to other sugar nucleotides.
Neose’s GlycoPEGylation program is enabling it to develop new protein drugs with improved half-life, while preserving the drug’s activity.
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