Photoswitching Affinity and Mechanism of Multivalent Lectin Ligands. Issue 27 (5th April 2022)

• Record Type: Journal Article
• Authors: Osswald, Uwe; Boneberg, Johannes; Wittmann, Valentin
• Is Part Of: Chemistry. Volume 28:Issue 27(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-05
• Subjects: carbohydrates -- lectins -- multivalency -- photochemistry -- proteins; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202200267
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Multivalent receptor–ligand binding is a key principle in a plethora of biological recognition processes. Immense binding affinities can be achieved with the correct spatial orientation of the ligands. Accordingly, the incorporation of photoswitches, which can be used to reversibly change the spatial orientation of molecules, into multivalent ligands is a means to alter the binding affinity and possibly also the binding mode of such ligands. We report a divalent ligand for the model lectin wheat germ agglutinin (WGA) containing an arylazopyrazole photoswitch. This switch, which has recently been introduced as an alternative to the more commonly used azobenzene moiety, is characterized by almost quantitative E / Z photoswitching in both directions, high quantum yields, and high thermal stability of the Z isomer. The ligand was designed in a way that only one of the isomers is able to bridge adjacent binding sites of WGA leading to a chelating binding mode. Photoswitching induces an unprecedentedly high change in lectin binding affinity as determined by isothermal titration calorimetry (ITC). Furthermore, additional dynamic light scattering (DLS) data suggest that the binding mode of the ligand changes from chelating binding of the E isomer to crosslinking binding of the Z isomer. Abstract : An arylazopyrazole‐containing divalent ligand was tailored to control multivalent binding to the model lectin wheat germ agglutinin (WGA) by light irradiation. The ligand was designed in such a way that only the E isomer is able to bridge adjacent binding sites of WGA. The two photoisomers show an unprecedentedly high change in binding affinity, as determined by isothermal titration calorimetry and different binding modes (chelating binding for the E isomer and crosslinking binding for the Z isomer).