Synthesis of Diverse Asparagine Linked Oligosaccharides

Abstract

Oligosaccharides are linked to the protein surface and play roles in a number of biological events.1,2) Therefore, much attention is being paid to research to investigate the function of the oligosaccharides. For post and co translational modification, attaching of oligosaccharides onto the proteins is thought to have a large effect on protein working. Recently, the human genome has been almost decoded, so that post genome research also requires a scrupulous study of the function of oligosaccharides on a protein.Oligosaccharides on glycoprotein are roughly divided into two groups, O linked and N linked types. In the case of the O linked type, a small oligosaccharide attaches to the alcohol of serine or threonine by an N acetyl D galactosaminyl linkage. The sequences of the small oligosaccharides are classified into 8 groups. On the other hand, the N linked type is a large branched oligosaccharide, which is further divided into three types: complex, hybrid, and high mannose type (Fig. 1). All oligosaccharides are linked to the nitrogen of asparagine by an N glycosyl linkage. Biosynthesis of this N linked oligosaccharide has been extensively studied. Recently, research for quality control of glycoprotein in the Endoplasmic reticulum has proved that a chaperon, calnexin calreticurin, monitors the folding process of protein recognizing high mannose type oligosaccharide on its protein surface and unfolded glycoproteins are then transported into a cytosol for digestion. 3)In order to prove the function of N glycan on the protein surface, a convenient synthetic method for N glycan and its glycopeptide should be developed. In this paper, we introduce recent synthetic developments focusing on the enzymatic synthesis of N linked oligosaccharides. Synthesis of N-linked oligosaccharide.During the synthesis of N linked oligosaccharide, several synthetic hindrances should be overcome such as stereo specific glycoside formation, and the reduction of repetitive protection and deprotection steps. In the case of glycosylation, formation of mannosyl and sialyl linkages, which is difficult, should be performed. Both glyco-* Fax. 81 45 787 2413, E mail: kajihara@yokohama cu.ac.jp J. Appl. Glycosci., 52, 177 182 (2005) ! C 2005 The Japanese Society of Applied Glycoscience Proceedings of the Symposium on Amylases and Related Enzymes, 2004Synthesis of Diverse Asparagine Linked Oligosaccharides (Received December 17, 2004) Yasuhiro KajiharaGraduate School of Integrated Science, Yokohama City University (22 2, Seto, Kanazawa ku, Yokohama 236 0027, Japan) Abstract: Oligosaccharides are linked to the protein surface and play roles in a number of biological events. Therefore, much attention is being paid to research to investigate the function of the oligosaccharides. In order to investigate the function of oligosaccharides, many synthetic approaches have been examined by synthesizing N-linked oligosaccharides. In this paper, we introduce recent synthetic developments focusing on the synthesis of N-linked oligosaccharides.