Fluorinated Carbohydrates as Lectin Ligands: Synthesis of OH/F‐SubstitutedN‐Glycan Core Trimannoside and Epitope Mapping by 2D STD‐TOCSYreF NMR spectroscopy

Abstract

Glycan‐protein interactions play an important role in a broad range of physiological processes, raising interest to elucidate the structural interplay. Yet, their dynamic nature limits the analysis by crystallography, whereas NMR spectroscopy suffers from the low 1H dispersion of glycans. Therefore, their sparse fluorination and NMR screening by 1D Saturation Transfer Difference with relay to 19F (STDreF) was previously proposed to exploit the superior dispersion in 19F NMR spectroscopy. A new 2D STD‐TOCSYreF experiment is presented here that enables comprehensive epitope mapping of fluorinated glycans by combining the spectral resolution of 19F with the spatial resolution and coverage of 1H. For an illustration, the 2‐deoxy‐2‐fluoro derivative of the N‐glycan core trimannoside was synthesised and its recognition of Pisum sativum agglutinin by either of the two terminal mannose residues was confirmed. Going beyond the crystallographic information, the 2D STD‐TOCSYreF spectrum moreover visualised collateral contacts from the branching mannose and allowed to assess the ratio of both co‐existing binding modes through the α1,3‐ (67 %) and α1,6‐linked (33 %) terminal mannose moieties.

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

“…Consequently, the synthesis of fluoro‐, deoxy‐, and thio‐glycosides is of high interest. In this context, we have sought to replace the hydroxyl groups of carbohydrates with fluorine atoms to generate new fluorine‐substituted glycoside analogues . The rationale for synthesizing such compounds stems from the similarity between the hydroxyl group and a fluoro substituent in terms of polarity and steric demand .…”

“…In this context, we have soughtt or eplace the hydroxyl groups of carbohydrates with fluorine atoms to generate new fluorine-substituted glycoside analogues. [10] The rationale for synthesizings uch compounds stems from the similarity between the hydroxyl group and a fluoro substituent in terms of polarity and steric demand. [11] Also, the loss of hydrogen-donating capacity for the fluorine atom and the high CÀFb ond energy render them resistantt o rapid in vivo degradation.…”

Materials science based on synthetic polysaccharides

“…27 The specific substitution of some hydroxyl groups with the isosteric fluorine shed light on the role of the replaced hydroxyl group in the overall conformation stabilization 21 and interaction with protein receptors. 28 The targeted OH/F substitution is a tool to map the hydrogen bonds required to stabilize a particular conformation. On the other hand, deoxyfluorination can also tune the oligosaccharide interactions with water molecules, suggesting that OH/F substitutions can have a profound effect on the glycan conformation.…”

Exploring the Chemistry of Non‐sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d‐Allopyranose

“…[15] Finally,t he groups of Diercks and Gabius prepared af luoro-N-glycanc ore trimannoside 7. [16] Its recognition to Pisum sativum was confirmed to be via the two terminal mannoser esidues.E xamples presentedi nF igure1 strongly suggest that more research should be directed toward the development of new strategies for the design of fluorinated carbohydratemimetics.…”

“…It is important to point out that the preparation of such fluorinated immunogenic tools is highly challenging and a flow procedure was developed to allow a scale‐up synthesis of fluorinated antigens . Finally, the groups of Diercks and Gabius prepared a fluoro‐ N ‐glycan core trimannoside 7 . Its recognition to Pisum sativum was confirmed to be via the two terminal mannose residues.…”