PEGylation involves covalently attaching polyethylene glycol (PEG) chains to peptide. Conjugation to macromolecular PEG improves the pharmacokinetics of the peptides by increasing the molecular mass of the peptide. This lowers the rate of peptide degradation by proteolytic enzymes, lowers clearance rates by the kidneys and increases the circulating half-life. PEG may also improve solubility and stability of the drug and is known to reduce toxicity and antigenicity. PEGylated drugs can also improve patient compliance by reducing the number of inconvenient, invasive injections.
PEG can be purchased from numerous sources. Because the long-chain PEGs typically used for manufacturing long-acting release (LAR) forms of peptides are heterogenous, both the polydisperse PEG conjugates and starting materials require analysis by sophisticated analytical techniques.
Short-chain monodisperse PEGs are also often used in peptide chemistry to provide spacers and linkers between peptides or between peptides and other molecules.
The PolyPeptide Group has significant experience PEGylating peptides under cGMP using a variety of different linker technologies, which include conjugation to thiol groups using maleimide and iodoacetate strategies and to primary amines using N-hydroxysuccinimide. We have experience with linear and branched monofunctional and bifunctional PEGS, as well conjugating multiple PEGs to single peptide sequences.
The Group has developed a range of product-specific analytical techniques to enable full characterization of the starting materials and final conjugate.