PEGylation of Carbohydrates Residues

The related PEGylation of aldehyde groups with PEG-amines is difficult since the -NH groups of proteins show a similar reactivity to the -NH group of PEG-amine, a fact which can result in the unwanted crosslinking of the protein. The pKa of hydrazides is around 3, allowing for selective conjugation at acidic pHs, at which most of the protein amino acids are in the protonated non-nucleophilic form (pKa aroxmd 10). 

Serine- or threonine-terminated proteins can be oxidized to the corresponding gly-oxylyl groups, which can then be reacted with aminooxy mPEG derivatives to achieve site-selective PEGylation. Furthermore, the reactive terminal carbonyl group can be introduced by metal catalyzed transamination [232]. 

---