Conformation‐Determining role for the N‐acetyl group in the O‐glycosidic linkage, α‐GalNAc‐Thr

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Abstract
An 1H‐nmr study of 2‐acetamido‐2‐deoxy‐3,4,6‐tri‐O‐acetyl‐D‐galactopyranose (AcGalNAc) glycosylated Thr‐containing tripeptides in Me2SO‐d6 solution reveals two mutually exclusive intramolecular hydrogen bonds. In Z‐Thr(AcGalNAc)‐Ala‐Ala‐OMe, there is an intramolecular hydrogen bond between the Thr amide proton and the sugar N‐acetyl carbonyl oxygen. The strength of this hydrogen bond will be dependent on the amino acid residues on the Thr C terminal side to some undetermined distance. In Ac‐Thr(AcGalNAc)‐Ala‐Ala‐OMe, a different intramolecular hydrogen bond between the sugar N‐acetyl amide proton and the Thr carbonyl oxygen exists. The choice of hydrogen bonds seems dependent on the bulkiness of the residues on the Thr N terminal side. The consequence of such strong hydrogen bonds is a clearly defined orientation of the sugar moiety with respect to the peptide backbone. In the former, the plane of the sugar pyranose ring is roughly oriented perpendicularly to the peptide backbone. The latter orientation is where the plane of the sugar ring is roughly in line with the peptide backbone. In both orientations, the sugar moiety can increase the shielding of the neighboring amino acid residues from the solvent. The idea that the amino acid residues near the glycosylated Thr influence orientation of the sugar moiety with respect to the peptide backbone and in turn possibly hinder peptide backbone flexibility has interesting implications in the conformational as well as the biological role of O‐glycoproteins.