Two New Fucose-\u03b1 (1\u20132)-Glycans Assigned In The Healthy Human Brain Taking The Number To Seven

Nathan Tosh,Carolyn Mountford,Graham Galloway,Scott Quadrelli

doi:10.1038/s41598-019-54933-1

Nathan Tosh, Carolyn Mountford + Show 2 more

Open Access

https://doi.org/10.1038/s41598-019-54933-1

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Abstract

Fucosylated glycans are involved in the molecular mechanisms that underpin neuronal development, learning and memory. The capacity to study the fucose-α(1–2)-glycan residues noninvasively in the human brain, is integral to understanding their function and deregulation. Five fucose crosspeaks were assigned to fucosylated glycans using invivo two-dimensional magnetic resonance Correlated SpectroscopY (2D L-COSY) of the brain. Recent improvements encompassed on the 3T Prisma (Siemens, Erlangen) with a 64-channel head and neck coil have allowed two new assignments. These are Fuc VI (F2:4.44, F1:1.37 ppm) and Fuc VII (F2: 4.29, F1:1.36 ppm). The Fuc VI crosspeak, close to the water resonance, is resolved due to decreased T1 noise. Fuc VII crosspeak, located between Fuc I and III, is available for inspection due to increased spectral resolution. Spectra recorded from 33 healthy men and women showed a maximum variation of up to 0.02 ppm in chemical shifts for all crosspeaks.

Highlights

Α-L-fucose residues, like α-L-N-acetyl neuraminic acid residues, are usually located at the non-reducing terminal position in an oligosaccharide chain
A typical 2D L-COSY spectrum obtained on a Siemens TRIO with an eight-channel head and neck coil is shown in Fig. 1A where the band of T1 noise around the water signal is seen to cover approximately 0.5 ppm
The same 2D L-COSY protocol collected with a Siemens Prisma with a 64 channel head and neck coil is shown in Fig. 1B where minimal T1 noise from the water signal band is seen to cover approximately 0.1 ppm, which permits a closer inspection of the region where the fucosylated glycans resonate

Summary

Introduction

Α-L-fucose residues, like α-L-N-acetyl neuraminic acid residues, are usually located at the non-reducing terminal position in an oligosaccharide chain. Five fucose-α(1–2)-galactose sugars (glycans) and free α-L-fucose substrate have been assigned in vivo in the human brain using the 2D L-COSY pulse sequence. The cross peaks Fuc I to Fuc VII reflect the scalar coupling between the C6-methyl groups and the protons attached to C5 of individual terminal fucose residues They were initially identified in the literature by their structures and conformational differences found in the blood group antigens carrying terminal fucose regions. They were initially identified in the literature by their structures and conformational differences found in the blood group antigens carrying terminal fucose regions3,4 This literature may explain the wide range of chemical shifts of the fucose-α(1–2)-glycans observed in the human brain. There was a 48% and 41% increase in fucosylated glycan Fuc IV, and Fuc VI, respectively

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