Structural Determination and Chemical Synthesis of the N‐Glycan from the Hyperthermophilic Archaeon Thermococcus kodakarensis

Abstract Asparagine‐linked protein glycosylations ( N ‐glycosylations) are one of the most abundant post‐translational modifications and are essential for various biological phenomena. Herein, we describe the isolation, structural determination, and chemical synthesis of the N ‐glycan from the hyperthermophilic archaeon Thermococcus kodakarensis . The N ‐glycan from the organism possesses a unique structure including myo ‐inositol, which has not been found in previously characterized N ‐glycans. In this structure, myo ‐inositol is highly glycosylated and linked with a disaccharide unit through a phosphodiester. The straightforward synthesis of this glycan was accomplished through diastereoselective phosphorylation and phosphodiester construction by S N 2 coupling. Considering the early divergence of hyperthermophilic organisms in evolution, this study can be expected to open the door to approaching the primitive function of glycan modification at the molecular level.