Pegylation of proteins and bioactive substances for medical and technical applications

Proteins and bioactive substances can be modified by chemically binding a synthetic macromolecule, polyethylene glycol (PEG), to the surface of these biomolecules. This can counter some of the drawbacks of native proteins and bioactive substances and improve their properties, which can be important for their use as protein drugs and catalysts in bioreactors. The most important problem is endowing delicate proteins with new suitable properties by chemical modification without causing any loss of their functions. In the medical applications of PEG-proteins, this review deals with anticancer proteins, antiinflammation proteins, blood proteins, antithrombosis proteins and others. These conjugates have unique properties; a reduction of immunoreactivity and immunogenicity, a prolongation of clearance time and an induction of immune tolerance. In biotechnological applications, this review has focused on the synthesis of unstable and/or chiral compounds using PEG-enzymes which are soluble and active in hydrophobic media such as benzene and chlorinated hydrocarbons. In fact, the reverse reactions of hydrolysis proceeds effectively with PEG-lipase and PEG-proteases to form ester and peptide bonds in organic solvents. Chemical modification has also been applied to liposomes, enzyme cofactors and other species. This approach will open new avenues for the development of useful biomedical, pharmacological and biotechnological processes. Copyright © 1998 Elsevier Science Ltd. All rights reserved.