Carbohydrate PEGylation in Chemotherapy

AGUSTI R.; MUCHNIK DE LEDERKREMER, R; GIORGI, ME

Recent Progress in Glycotherapy

Bentham Science Publishers

Lugar: Sharjah; Año: 2016; p. 60 - 101

Improvement of drug delivery by covalent modification with polyethyleneglycol (PEG) has been widely applied to proteins and low molecular weightpharmaceuticals. Protein therapeutic agents have the drawback of short circulatinghalf-life due to their lability towards proteolytic enzymes and rapid clearance by kidneyfiltration. Moreover, their recognition by the immune system results in the productionof neutralizing antibodies. Several strategies have been used for the PEGylation ofproteins at the amino group of lysine but the product is heterogeneous due to randomPEGylation. More recently, selective PEGylation of proteins was achieved byintroduction of a PEGylated carbohydrate in an O-glycosylation site. This technique iscalled glycoPEGylation and is used for the production of several therapeutics, some ofthem are currently in advanced clinical trials. Improvement of the delivery systemrather than the drug itself has led to the optimization of the therapeutic properties ofexisting drugs by minimizing their side effects. In this respect, active targeting toreceptors present in cancer tissues prevents healthy ones from being damaged. Sincecarbohydrates have been recognized as playing an important role in the interaction withcell receptors, PEGylated carbohydrates have been used for active targeting of drugs. Inthis review we discuss different applications of sugar-PEGylation