Protein PEGylation

Abstract

The covalent linking of poly(ethylene glycol) (PEG) has become the leading approach to improving the therapeutic effi cacy of proteins. This highly hydrophilic synthetic polymer possesses unique properties that allowed PEG to emerge as the best candidate for protein modifi cation. Beside the proven success of PEG conjugates already on the market, it should be noted that other derivatives are presently under advanced clinical trials. The increased half-life of the conjugates is probably the main reason for performing PEGylation. In addition, the possibility to greatly reduce the immunogenicity of a given protein is also a strong and determinant incentive. This last advantage offers the possibility to safely use, in the clinic, heterologous proteins that otherwise might trigger dramatic immunogenic responses or even anaphylactic reactions. This chapter introduces the reader to PEGylation strategies showing in detail its potential and the achievements obtained in the recent years. Furthermore, the future perspectives of the technique are also discussed.

Robust and Degradable Hydrogels from Poly(ethylene glycol) and Semi-Interpenetrating Collagen

“…PEG based hydrogels ,,, have been evaluated for materials used in disposable devices, sensors and actuators, and microfluidics and as scaffolds for tissue repair and for sealants. − Advantages of using PEG include its bioinert nature, biocompatibility, hydrophilicity, low protein adsorption, and versatility when being chemically modified. ,,, PEG is widely available and most often used in its linear form. Linear PEG macromolecules have hydroxyl end groups that, using the appropriate chemistry, can be modified with acrylates, amines, maleimide, and aldehyde functionalities thereby changing the chemical, physical, and biological properties. , PEG–diacrylate (PEGDA) is a very common form that has been used to form cross-linked rigid hydrogels. ,,− Cells can be encapsulated into these PEGDA networks; and the PEG can be functionalized e.g. with lactides to allow for cell adhesion, proliferation, , and degradability .…”

“…Linear PEG macromolecules have hydroxyl end groups that, using the appropriate chemistry, can be modified with acrylates, amines, maleimide, and aldehyde functionalities thereby changing the chemical, physical, and biological properties. 35,36 PEG− diacrylate (PEGDA) is a very common form that has been used to form cross-linked rigid hydrogels. 11,17,37−39 Cells can be encapsulated into these PEGDA networks; 40 and the PEG can be functionalized e.g.…”