Peptide and protein PEGylation: a review of problems and solutions

The paper discusses general problems in using PEG for conjugation to high or low molecular weight molecules. Methods of binding PEG to different functional groups in macromolecules is reported together with their eventual limitations. Problems encountered in conjugation, such as the evaluation of the number of PEG chains bound, the localisation of the site of conjugation in polypeptides and the procedure to direct PEGylation to the desired site in the molecule are discussed. Finally, the paper reports on more specific methods regarding reversible PEGylation, cross-linking reagents with PEG arms, PEG for enzyme solubilization in organic solvent and new polymers as alternative to PEG.