Anomeric memory of the glycosidic bond upon fragmentation and its consequences for carbohydrate sequencing

Abstract

Deciphering the carbohydrate alphabet is problematic due to its unique complexity among biomolecules. Strikingly, routine sequencing technologies—which are available for proteins and DNA and have revolutionised biology—do not exist for carbohydrates. This lack of structural tools is identified as a crucial bottleneck, limiting the full development of glycosciences and their considerable potential impact for the society. In this context, establishing generic carbohydrate sequencing methods is both a major scientific challenge and a strategic priority. Here we show that a hybrid analytical approach integrating molecular spectroscopy with mass spectrometry provides an adequate metric to resolve carbohydrate isomerisms, i.e the monosaccharide content, anomeric configuration, regiochemistry and stereochemistry of the glycosidic linkage. On the basis of the spectroscopic discrimination of MS fragments, we report the unexpected demonstration of the anomeric memory of the glycosidic bond upon fragmentation. This remarkable property is applied to de novo sequencing of underivatized oligosaccharides.

The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human

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“…While reversed-phase separations remain the preferred choice in glycan separations, HILIC or normal stationary phases have seen some recent use 2 . Even with the growing suite of MS n methods, the deconvolution and identification of co-eluting species remains a challenge since isomers exhibit very similar fragmentation pathways 4 , 5 . Additionally, while spectroscopic approaches have shown promise for glycan fingerprinting, these methods remain of limited utility for accurately characterizing isomeric mixtures 6 .…”

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