A Secondary Structural Element in a Wide Range of Fucosylated Glycoepitopes

Abstract

The increasing understanding of the essential role of carbohydrates in development, and in a wide range of diseases fuels a rapidly growing interest in the basic principles governing carbohydrate-protein interactions. A still heavily debated issue regarding the recognition process is the degree of flexibility or rigidity of oligosaccharides. Combining NMR structure determination based on extensive experimental data with DFT and database searches, we have identified a set of trisaccharide motifs with a similar conformation that is characterized by a non-conventional C-H⋅⋅⋅O hydrogen bond. These motifs are present in numerous classes of oligosaccharides, found in everything from bacteria to mammals, including Lewis blood group antigens but also unusual motifs from amphibians and marine invertebrates. The set of trisaccharide motifs can be summarized with the consensus motifs X-β1,4-[Fucα1,3]-Y and X-β1,3-[Fucα1,4]-Y-a secondary structure we name [3,4]F-branch. The wide spectrum of possible modifications of this scaffold points toward a large variety of glycoepitopes, which nature generated using the same underlying architecture.

(3, 2)D 1H, 13C BIRDr,X-HSQC-TOCSY for NMR structure elucidation of mixtures: application to complex carbohydrates

“…In the native polysaccharide, the fucose ring is stacked above the neighbouring GlcNAc residue enabling formation of an unusual hydrogen bond from its H5 proton to the ring oxygen of GalNAc, as described previously (Panagos et al 2014;Aeschbacher et al 2017). β-elimination breaks the GalNAc(1→4)GlcA glycosidic bond, transforming fucose into a terminal unit of the newly formed oligosaccharides II and IV.…”

Three-Dimensional Structures of Carbohydrates and Where to Find Them

“…Advances in NMR methods hold great potential for direct spatial structure determination of carbohydrate-protein complexes in solution based on intermolecular NOEs which affords estimation of atomic contacts between a protein and a carbohydrate ligand [ 97 , 98 ]. Further extraction of NOE-derived distance restraints for a saccharide molecule results in generation of representative conformational ensembles [ 99 , 100 , 101 ].…”

Silber‐ und Bronzemedaillen des CNRS in Chemie 2019

“…Außerdem wirkt er an der Entwicklung von Nanosensoren und funktionalisierbaren fluoreszierenden Polymernanopartikeln für biologische Bildgebung und Theranostik mit. Collot berichtete vor kurzem in einem Beitrag in Chemistry—A European Journal über ein Sekundärstrukturelement in fucosylierten Glykoepitopen …”