CHEMISTRY OF POLYETHYLENE-GLYCOL CONJUGATES WITH BIOLOGICALLY-ACTIVE MOLECULES

Polyethylene glycol (PEG) is widely used as a covalent modifier of biological macromolecules and particulates as well as a carrier for low molecular weight drugs. In the first two instances proteins and liposomes are of particular importance. Their conjugates with PEG often possess the ability to avoid quick recognition and clearance in vivo, that their unconjugated counterparts are suffering from. In this review (with 133 references) methods for preparation of PEG conjugates with various biologically active compounds are summarized. Since the bulb of the published work in this held involves proteins, drugs, and lipids, an appropriate emphasis is given to the conjugates of these compounds. While the first two types of PEG conjugates are usually intended for a direct use as therapeutics, PEG-lipids are mainly utilized for formation of long-circulating liposomes. Particular attention is paid to the comparative attributes of various reactive PEG derivatives, properties of the linkages formed, and possible side reactions. The relationships between various conjugation strategies and their influence on the relevant biological properties and/or on in vivo performance of the corresponding conjugates is also discussed.