Peptides play a key role in the pharmaceutical industry and drug therapeutic development; however, their in vivo applications are sometimes limited due to fast degradation by proteases, poor solubility, antigenic responses, and glomerular filtration in the kidney. The covalent attachment of polyethylene glycol (PEG) chains to peptides is one approach that, in some peptide-PEG conjugates, to reduce immunogencity, improve solubility, and reduce renal clearance. Short (n = 2 to 20) monodispersed PEG chains can also be used as spacers or linkers between the peptide and other bio- or small molecules.
CPC Scientific can perform PEGylation modifications at various sites of a peptide. N-terminal PEGylation can be accomplished by direct PEG carboxylic acid coupling or native chemical ligation with PEG thioester and a cysteine residue in the peptide. C-terminal is more complicated, but can be achieved through a thiocarboxylic acid modification and sulfone-azide PEG reagent. Hydrazide modifications combined with a pyruvoyl PEG reagent is also a useful approach to C-terminal PEGylation. In addition to the N- and C-terminal, PEGylation is also possible at virtually any amino acid side chain bearing the appropriate functional group. In this context, three methodologies are often used for site-specific PEGylations:
- Click Chemistry, which takes place between an azide group of the PEG reagent and an alkyne group of the peptide, or vice versa.
- Sonogashira Coupling, which takes place between an iodophenyl group of the PEG reagent and an alkyne group of the peptide, or vice versa.
- Suzuki-Miyaura Coupling, with takes place between the iodophenyl group of PEG reagent and an aryl borinic acid group of peptide, or vice versa.
|ABBREV.||FULL PEG CHAIN NAME|
|PEG750||Poly(ethylene glycol) methyl ether (average Mn 750)|
|PEG1000||Poly(ethylene glycol) methyl ether (average Mn 1000)|
|PEG2000||Poly(ethylene glycol) methyl ether (average Mn 2000)|
|PEG5000||Poly(ethylene glycol) methyl ether (average Mn 5000)|