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 of misfolded 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. 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 common precursorwas developed to facilitate more comprehensive analysis of glycan functions in the GQC. In addition, using the glycan library and ultrafiltration membrane combined with HPL Canalyses, a simple method for quantification of protein–ligand interaction was established.