Protein PEGylation, basic science and biological applications

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A historical overview of protein-polymer conjugation is reported here, demonstrating the superiority of poly(ethylene glycol) (PEG) among other synthetic or natural polymers, thanks to its unique properties like the absence of toxicity and immunogenicity, and a high solubility in water and in organic solvents. Furthermore, PEG is approved by the FDA for human use. Relevant physicochemical and biological properties of PEG and PEG-conjugates, as the basis of the pharmacokinetic and pharmacodynamic improvements, are reported here and discussed in view of successful therapeutic applications. The chapter also highlights that, although PEGylation is well studied and exploited by many researchers from both academia and industry, it remains difficult to forecast its effects on a predetermined bioactive molecule. The use of PEG-enzymes in bioconversion, which is of interest in drug discovery and production, is also briefly reported.