A Photoswitchable Trivalent Cluster Mannoside to Probe the Effects of Ligand Orientation in Bacterial Adhesion

Abstract

We have recently demonstrated, by employing azobenzene glycosides, that bacterial adhesion to surfaces can be switched through reversible reorientation of the carbohydrate ligands. To investigate this phenomenon further, we have turned here to more complex—that is, multivalent—azobenzene glycoclusters. We report on the synthesis of a photosensitive trivalent cluster mannoside conjugated to an azobenzene hinge at the focal point. Molecular dynamics studies suggested that this cluster mannoside, despite the conformational flexibility of the azobenzene‐glycocluster linkage, offers the potential for reversibly changing the glycocluster's orientation on a surface. Next, the photoswitchable glycocluster was attached to human cells, and adhesion assays with type 1 fimbriated Escherichia coli bacteria were performed. They showed marked differences in bacterial adhesion, dependent on the light‐induced reorientation of the glycocluster moiety. These results further underline the importance of orientational effects in carbohydrate recognition and likewise the value of photoswitchable glycoconjugates for their study.

Photoswitching Affinity and Mechanism of Multivalent Lectin Ligands

“…Soluble monovalent mannose‐substituted azo‐benzene derivatives were investigated for their potency to inhibit the adhesion of type 1‐fimbriated Escherichia coli to mannan‐coated microtiter plate surfaces [18] . Although this experimental setup did not lead to different IC 50 values for the E and Z isomers, immobilization of glycosylated azo‐benzene derivatives on microtiter plates [19] or human cell membranes [20] resulted in photoswitchable surfaces that showed marked differences in bacterial adhesion, dependent on the light‐induced configuration of the glycosylated azo‐benzene moiety. These findings underline the significance of orientation of carbohydrate ligands for efficient multivalent recognition by lectins.…”

Cover Feature: Photoswitching Affinity and Mechanism of Multivalent Lectin Ligands (Chem. Eur. J. 27/2022)

“…Soluble monovalent mannose-substituted azo-benzene derivatives were investigated for their potency to inhibit the adhesion of type 1fimbriated Escherichia coli to mannan-coated microtiter plate surfaces. [18] Although this experimental setup did not lead to different IC 50 values for the E and Z isomers, immobilization of glycosylated azo-benzene derivatives on microtiter plates [19] or human cell membranes [20] resulted in photoswitchable surfaces that showed marked differences in bacterial adhesion, dependent on the light-induced configuration of the glycosylated azobenzene moiety. These findings underline the significance of orientation of carbohydrate ligands for efficient multivalent recognition by lectins.…”

Advances in Application of Azobenzene as a Trigger in Biomedicine: Molecular Design and Spontaneous Assembly

“…Compared with azobenzene derivatives containing only one ligand, the multivalent ligand has the ability to improve the recognition of cells or proteins. As a typical case, Lindhorst [ 199 ] and colleagues synthesized and used more complex multivalent‐azobenzene glycoclusters to regulate bacterial adhesion to surfaces. Photoswitchable cluster mannosides were prepared by the coupling of trivalent cluster mannosides and click chemistry with azobenzene units.…”