Photoswitchable, Water‐Soluble Bisazobenzene Cross‐Linkers with Enhanced Properties for Biological Applications

• Published in: ChemPhotoChem Vol. 6; no. 12
• Main Authors: Volarić, Jana, Thallmair, Sebastian, Feringa, Ben L., Szymanski, Wiktor
• Format: Journal Article
• Language: English
• Published: 01.12.2022
• Subjects: bisazobenzene; photostationary states; photoswitches; protein function; protein-protein interactions; water-solubility
• ISSN: 2367-0932; 2367-0932
• DOI: 10.1002/cptc.202200170

Photoswitchable cross‐linkers are light‐responsive molecules that can be attached at two locations to a target biomolecule to modulate its activity. Under irradiation, the cross‐linker changes the distance between the residues it spans, affecting the structure and function of the labeled target. Efficient photocontrol is enabled especially by cross‐linkers with large end‐to‐end length change upon switching. The design of water‐soluble azobenzene‐based cross‐linkers for applications in chemical biology remains challenging due to major issues regarding synthesis and purification. Furthermore, the solubility and photochemical properties of the reported systems are frequently not suitable in aqueous media. Herein we report two water‐soluble bisazobenzene cross‐linkers with extended half‐lives and high photostationary state isomer distributions that can be achieved upon irradiation. We present molecules that enable cross‐linking of biomolecular residues within one target, or are bridging two proteins to allow the study of protein–protein interactions, which paves the way for light‐based manipulation of under‐explored biological targets. Photoswitchable cross‐linkers have the ability to connect two residues on a biomolecule, thereby causing large changes in the structure and function of the target upon irradiation. The design, synthesis and purification of cross‐linkers with large end‐to‐end distances remains challenging, especially for applications in chemical biology. Herein we describe two water‐soluble bisazobenzene cross‐linkers featuring enhanced photochemical properties in an aqueous environment.