Premium
Synthesis of Glc 1 Man 9 ‐Glycoprotein Probes by a Misfolding/Enzymatic Glucosylation/Misfolding Sequence
Author(s) -
Izumi Masayuki,
Oka Yukiho,
Okamoto Ryo,
Seko Akira,
Takeda Yoichi,
Ito Yukishige,
Kajihara Yasuhiro
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201511491
Subject(s) - glycoprotein , calreticulin , biochemistry , chemistry , glycan , glycosylation , lectin , enzyme , sequence (biology) , endoplasmic reticulum
Glycoproteins in non‐native conformations are often toxic to cells and may cause diseases, thus the quality control (QC) system eliminates these unwanted species. Lectin chaperone calreticulin and glucosidase II, both of which recognize the Glc 1 Man 9 oligosaccharide on glycoproteins, are important components of the glycoprotein QC system. Reported herein is the preparation of Glc 1 Man 9 ‐glycoproteins in both native and non‐native conformations by using the following sequence: misfolding of chemically synthesized Man 9 ‐glycoprotein, enzymatic glucosylation, and another misfolding step. By using synthetic glycoprotein probes, calreticulin was found to bind preferentially to a hydrophobic non‐native glycoprotein whereas glucosidase II activity was not affected by glycoprotein conformation. The results demonstrate the ability of chemical synthesis to deliver homogeneous glycoproteins in several non‐native conformations for probing the glycoprotein QC system.