Glycochemical Synthesis by Hung Shang-Cheng Zulueta Medel Manuel L. & Medel Manuel L. Zulueta

Author:Hung, Shang-Cheng,Zulueta, Medel Manuel L. & Medel Manuel L. Zulueta
Language: eng
Format: epub
ISBN: 9781119006473
Publisher: John Wiley & Sons, Inc.
Published: 2016-10-17T00:00:00+00:00

11

CHEMICAL GLYCOPROTEIN SYNTHESIS

Yasuhiro Kajihara1, Masumi Murakami1, and Carlo Unverzagt2

1 Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan

2 Bioorganische Chemie, Universität Bayreuth, Bayreuth, Germany

11.1 INTRODUCTION

Posttranslational modifications of proteins are critical biosynthetic steps, which can enhance or alter protein functions [1]. These extensively studied protein modifications regulate important biological events. Phosphorylation is involved in signal transduction, ubiquitination mediates proteolysis, attachment of fatty acids leads to membrane anchoring, and glycosylation assists in protein folding, trafficking, and protein–protein interactions [1]. Among these modifications, glycosylation not only is the major pattern but also provides a complex system for protein modifications. N‐Linked oligosaccharides consist of mannose‐rich structures in the endoplasmic reticulum (ER), which are later converted into acidic oligosaccharides in the Golgi apparatus. The composition of these oligosaccharides changes depending on the biosynthetic status of the glycoprotein. Nearly all proteins on the mammalian cell surface as well as in body fluids are glycosylated, and these glycoproteins play central roles in many critical biological events such as cell–cell recognition, immunity, and development [2]. Recent studies have revealed the cross talk between the N‐acetylglucosamine (GlcNAc) modification of serine (Ser) or threonine (Thr) and O‐phosphorylation [3].

In order to elucidate the many unknown functions of oligosaccharides in glycoproteins, numerous biological experiments have been carried out using glycoprotein substrates isolated from mammalian or eukaryotic sources. However, those isolated glycoproteins exhibit heterogeneous oligosaccharide structures, which frequently lead to ambiguous conclusions when trying to assign the contribution of an individual oligosaccharide structure to a biological event. This lack of substrates for research and therapy has stimulated chemists to prepare glycoprotein macromolecules exhibiting native three‐dimensional protein structures combined with uniform oligosaccharides. This chapter summarizes the recent synthetic methodologies enabling the preparation of glycoproteins bearing homogeneous oligosaccharides.

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