Design and synthesis of oligosaccharides that interfere with glycoprotein quality-control systems

Midori A. Arai, Ichiro Matsuo, Shinya Hagihara, Kiichiro Totani, Jun Ichi Maruyama, Katsuhiko Kitamoto, Yukishige Ito

研究成果: Article査読

29 被引用数 (Scopus)

抄録

Calnexin (CNX) and its soluble homologue calreticulin (CRT) are lectin-like molecular chaperones that help newly synthesized glycoproteins to fold correctly in the rough endoplasmic reticulum (ER). To investigate the mechanism of glycoprotein-quality control, we have synthesized structurally defined high-mannose-type oligosaccharides related to this system. This paper describes the synthesis of the non-natural undecasaccharide 2 and heptasaccharide 16, designed as potential inhibitors of the ER quality-control system. Each possesses the key tetrasaccharide element (Glc1Man3) critical for the CNX/CRT binding, while lacking the pentamannosyl branch required for glucosidase II recognition. These oligosaccharides were evaluated for their ability to bind CRT by isothermal titration calorimetry (ITC). As expected, each of them had a significant affinity towards CRT. In addition, these compounds were shown to be resistant to glucosidase II digestion. Their activities in blocking the chaperone function of CRT were next measured by using malate dehydrogenase (MDH) as a substrate. Their inhibitory effects were shown to correlate well with their CRT-binding affinities, both being critically dependent upon the presence of the terminal glucose (Glc) residue.

本文言語English
ページ(範囲)2281-2289
ページ数9
ジャーナルChemBioChem
6
12
DOI
出版ステータスPublished - 2005 12 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 有機化学

フィンガープリント

「Design and synthesis of oligosaccharides that interfere with glycoprotein quality-control systems」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル