CHEMISTRY OF POLYETHYLENE-GLYCOL CONJUGATES WITH BIOLOGICALLY-ACTIVE MOLECULES

Polyethylene glycol (PEG) is widely used as a covalent modifier of bio logical macromolecules and particulates as well as a carrier for low m olecular weight drugs. In the first two instances proteins and liposom es are of particular importance. Their conjugates with PEG often posse ss the ability to avoid quick recognition and clearance in vivo, that their unconjugated counterparts are suffering from. In this review (wi th 133 references) methods for preparation of PEG conjugates with vari ous biologically active compounds are summarized. Since the bulb of th e published work in this held involves proteins, drugs, and lipids, an appropriate emphasis is given to the conjugates of these compounds. W hile the first two types of PEG conjugates are usually intended for a direct use as therapeutics, PEG-lipids are mainly utilized for formati on 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 relationship s between various conjugation strategies and their influence on the re levant biological properties and/or on in vivo performance of the corr esponding conjugates is also discussed.