Abstract
High-mannose-type oligosaccharides, which are co-translationally introduced to nascent polypeptides, play important roles in protein quality control. This process is very complex, involving a number of lectins, chaperones and glycan processing enzymes. For example, calnexin (CNX) and calreticulin (CRT) are molecular chaperons that recognize mono-glucosylated form of high-mannose-type glycans. UDP-Glucose : glycoprotein glucosyltransferase (UGGT) only glucosylates high-mannose-type glycans of unfolded glycoproteins. Fbs 1 is a part of ubiquitin ligase that recognizes sugar chains. Although recent studies have clarified properties of these proteins, most of them used oligosaccharides derived from natural source, which contain structural heterogeneity. In order to gain a precise insight about protein quality control, we comprehensively synthesized high-mannose-type glycans associated with protein quality control system. Additionally, during our investigations of artificial glycoproteins having homogeneous oligosaccharides, a novel non-peptidic substrate for UGGT was discovered. Using these synthetic oligosaccharide probes, we quantitatively evaluated the activity of CRT, Fbs 1 and UGGT.
