Surface decoration of hemoglobin with polyethylene glycol

Conjugation of polymers to peptide and protein therapeutics to generate hybrid molecules with unique and distinct molecular properties has become a popular approach to alter and control their stability, biodistribution, pharmacokinetics, and toxicology. Polyethylene glycol (PEG) reagents of various sizes have been used for PEGylation. Although linear PEG reagents of various molecular sizes have been the choice molecules in the earlier studies, branched PEGs and very large linear PEG chains are now available, especially for site-specific PEGylation. PEGylation using these new large or branched PEGs has been referred to as advanced PEGylation. Polyethylene glycols are inert and nontoxic polymers. Accordingly, there has been significant interest in developing PEGylated protein therapeutics for clinical applications. Conjugation of the PEG chains to bovine serum albumin using 2,4,6-trichloro triazine activated PEG was the first study of modifying the protein with PEG, and multiple copies of PEG chains were attached to the protein. PEGylated bovine serum albumin is incapable of eliciting antibody to itself or the unmodified albumin; PEGylation of the protein has enabled it to camouflage itself from the immune system. Furthermore, the PEGylated albumin showed extended circulating life in the blood.