Protein, peptide and non-peptide drug PEGylation for therapeutic application

Abstract

For many years proteins have been investigated as therapeutic agents, but unfortunately their potential advantages could not be completely exploited. The main drawbacks are their intrinsic short life in the body, immunological adverse reaction and proteolytic digestion. Among all the approaches studied for overcoming these problems, PEGylation (the modification of molecules with polyethylene glycol [PEG]) achieved the most interesting results, leading to a novel series of products that have already reached the market, and hopefully other promising agents will soon be available. Since the first studies in this field, the conjugation of PEG to a protein has shown the possibility of improving the pharmacokinetic profile of a linked drug. In the last few years this technology, firstly developed for proteins, has been transferred to non-peptide drugs, opening a new area of investigation that is now receiving increasing interest. This leads to new opportunities for many therapeutic treatments as it is possible to use molecules that could not before be exploited due to limitations such as inadequate water solubility, high nonspecific toxicity and poor pharmacokinetic profiles. In this review the most recent achievements in PEGylation of protein, peptide and non-peptide drugs are described concerning the binding chemistry, and many examples from the literature are reported, in the fields of both protein therapeutics and non-peptide drugs.