Chemical modification of proteins with polyethylene glycols

Abstract

Proteins as well as bioactive substances were coupled with two types of polyethylene glycol (PEG) derivatives, one with a chain-shaped form, 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2), and the other with a comb-shaped form, copolymer of PEG and maleic anhydride (activated PM). This modification technique eliminated some of the drawbacks of the native proteins and bioactive substances and also endowed them with new functions. l-Asparaginase and bovine serum albumin caused a reduction of immunoreactivity toward their antibodies and a prolongation of the clearance time through this modification. The modified lipase catalyzed the reverse reaction of hydrolysis, ester synthesis and ester exchange reactions in the hydrophobic media. This technique was further extended to various kinds of bioactive substances to form magnetic urokinase, PEG2-melanin and chlorophyll-bentonite conjugates. These phenomena have been discussed in relation to the structures of the modifiers, PEGs and PMs.