ER Molecular Chaperone Interactions with Structurally Defined High-Mannose-Type Oligosaccharides

Abstract

Calnexin (CNX), and its soluble homologue calreticurin (CRT) are molecular chaperones that lead newly synthesized glycoproteins to correct folding structure in the endoplasmic reticulum (ER). To investigate the mechanism of protein quality control, we have synthesized structurally defined high-mannose-type oligosaccharides related to this ER system. Moreover, an undecasaccharide was designed and synthesized as a CNX/CRT inhibitor that possess key structural features of CNX/CRT binding without a recognized unit by a Glucosidase II, which removes glucose residue from the CNX/CRT binding structure to release from this chaperones. Their binding properties to CRT and inhibition activities of CRT's suppression of thermal aggregation of malate dehydrogenase (MDH) were investigated. Synthesized inhibitor showed the binding property to CRT and showed inhibition of CRT.

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