Protein glycosylation: implications for in vivo functions and therapeutic applications

The glycosylation machinery in eukaryotic cells is available to all proteins that enter the secretory pathway. There is a growing interest in diseases caused by defective glycosylation, and in therapeutic glycoproteins produced through recombinant DNA technology route. The choice of a bioprocess for commercial production of recombinant glycoprotein is determined by a variety of factors, such as intrinsic biological properties of the protein being expressed and the purpose for which it is intended, and also the economic target. This review summarizes recent development and understanding related to synthesis of glycans, their functions, diseases, and various expression systems and characterization of glycans. The second section covers processing of N- and O-glycans and the factors that regulate protein glycosylation. The third section deals with in vivo functions of protein glycosylation, which includes protein folding and stability, receptor functioning, cell adhesion and signal transduction. Malfunctioning of glycosylation machinery and the resultant diseases are the subject of the fourth section. The next section covers the various expression systems exploited for the glycoproteins: it includes yeasts, mammalian cells, insect cells, plants and an amoeboid organism. Biopharmaceutical properties of therapeutic proteins are discussed in the sixth section. In vitro protein glycosylation and the characterization of glycan structures are the subject matters for the last two sections, respectively.