# Fluorinated Glycan Frameshifts: Automated Synthesis Expedites the Study of Glycan‐Protein Interactions by 19F‐BioNMR

## TL;DR

This paper introduces a new method for synthesizing fluorinated glycans to study how they interact with proteins using 19F-BioNMR.

## Contribution

The paper introduces automated synthesis of fluorinated glycans and their use in studying glycan-protein interactions via 19F-BioNMR.

## Key findings

- Automated glycan assembly enabled stereoselective synthesis of fluorinated glycans.
- 19F-BioNMR analysis revealed frameshift-dependent binding patterns with ConA.
- Fluorinated glycans showed potential as probes for studying lectin interactions.

## Abstract

Given the prominence of 19F‐bioNMR in structural research, fluorinated glycan frameshifts hold enormous potential in studying carbohydrate‐protein interactions. To contribute to this field, the synthesis of selectively C‐2 fluorinated glycans related to the O3b antigen of Klebsiella pneumoniae is disclosed, and their interactions with the lectin Concanavalin A (ConA) are interrogated spectroscopically. Automated glycan assembly (AGA) was employed to expedite construction in which the C(sp3)‐F bond was leveraged to control stereoselectivity of α‐mannosylation. Subsequent 19F‐BioNMR analysis of binding to ConA allowed determination of the respective IC50 and K
D values; this revealed a conspicuous frameshift‐dependency in which one pattern dominated. Collectively, this study advocates for the strategic utilisation of the C(sp3)‐F bond in the design, construction, and analysis of probes to interrogate ubiquitous mannose‐binding lectins with therapeutic relevance.

Given the prominence of 19F‐bioNMR in structural research, fluorinated glycans hold enormous potential in glycomimetic frameshift design. However, challenges associated with the stereocontrolled synthesis of these disruptive actors continue to frustrate advances. To address this, the automated synthesis of selectively C‐2 fluorinated glycans related to the O3b antigen of Klebsiella pneumoniae is disclosed, and their interactions with the lectin Concanavalin A (ConA) are interrogated spectroscopically.