Synthetic Approach to Glycoprotein Quality Control System

Abstract

Glycoprotein quality control (GQC) in the endoplasmic reticulum involves many functions, including folding and transport of nascent proteins as well as degradation ofmisfolded proteins. Recent studies have revealed that high-mannose-type glycans which are recognized by lectins and various carbohydrate-processing enzymes in GQC process play critical roles. In order to provide quantitative information on the activity and specificity of GQC-related proteins with well-defined homogeneous glycans, a convergent synthesis of high-mannose-type glycans was achieved. Y. Ito (*) Synthetic Cellular Chemistry Laboratory, RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama, Japan ERATO, Japan Science and Technology Agency (JST), Ito Glycotrilogy Project, Wako, Saitama, Japan e-mail: yukito@riken.jp A. Seko • Y. Takeda ERATO Glycotrilogy Project, Japan Science and Technology Agency, Wako, Saitama, Japan e-mail: seko@glt.jst.go.jp; yotakeda@riken.jp # Springer Japan 2015 N. Taniguchi et al. (eds.), Glycoscience: Biology and Medicine, DOI 10.1007/978-4-431-54841-6_104 305 Subsequent derivatization of these glycans was shown to be versatile substrates of lectins and enzymes such as ER glucosidase II, UDP-Glc: glycoprotein glucosyltransferase (UGGT), and calreticulin. More recently, a high-mannose-type glycan library through “top-down” diversification of a commonprecursor was developed to facilitate more comprehensive analysis of glycan functions in the GQC. In addition, using the glycan library and ultrafiltrationmembrane combinedwithHPLCanalyses, a simple method for quantification of protein–ligand interaction was established.