# Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance

## TL;DR

This paper presents a new way to study how bacteria recognize sugars by using a molecule that can change shape to control the distance between two sugar-binding units.

## Contribution

The novel contribution is the use of a xylose-based conformational switch to modulate glycoligand distance and study its effect on bacterial adhesion inhibition.

## Key findings

- A xylopyranoside scaffold can switch conformations to control the spatial arrangement of mannoside ligands.
- Conformational changes affect the biological activity of bivalent glycoclusters in adhesion inhibition assays.
- Molecular modeling correlates ligand distance with the structure of the glycocluster–FimH complex.

## Abstract

Functional glycomimetics is suited to study the parameters of carbohydrate recognition that forms the basis of glycobiology. It is particularly attractive when a glycoligand allows for the investigation of two different states, such as varying distance between multiple glycoligands. Here, a xylopyranoside was employed as a scaffold for the presentation of two mannoside units which are ligands of the bacterial lectin FimH. The chair conformation of the central xyloside can be switched between a 4C1 and a 1C4 conformation whereby the two conjugated mannoside ligands are flipped from a di-equatorial into a di-axial position. Concomitantly, the distance between the two glycoligands changes and, as a consequence, so does the biological activity of the respective bivalent glycocluster, as shown in adhesion–inhibition assays with live bacteria. Molecular modeling was employed to correlate the inter-ligand distance with the structure of the formed glycocluster–FimH complex. Our study suggests that conformational switches can be employed and further advanced as smart molecular tools to study structural boundary conditions of carbohydrate recognition in a bottom-up approach.