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

Abstract

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 halflives 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 proteinprotein interactions, which paves the way for light-based manipulation of under-explored biological targets.

Vinyl Phosphonates as Photopharmacological Agents: Laser‐Induced Cis‐Trans Isomerization and Butyrylcholinesterase Activity

“…Nowadays, combinations of photoswitchers with antibiotics ( Vancomycin and Cephalosporin ), anti‐Alzheimer's medicine Takrin we successfully demonstrated [6,22,23] . Deep and detailed investigations by Trauner, Decker, Szymanski and many other groups demonstrate the potency of such approach for photopharmacology [8,24–26] …”

“…[6,22,23] Deep and detailed investigations by Trauner, Decker, Szymanski and many other groups demon-strate the potency of such approach for photopharmacology. [8,[24][25][26] Special attention of photopharmacology is focused on the design of photoswitchable inhibitors of two important esterases -acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These esterases are involved in the hydrolysis of the acetylcholine neurotransmitter and are connected with heavy human disorders -Alzheimer's disease, memory disorders, skin diseases (psoriasis, epithelial cell injuries, vitiligo, atopic dermatitis, etc).…”

E–Z Photoisomerization in Proton-Modulated Photoswitchable Merocyanine Based on Benzothiazolium and o-Hydroxynaphthalene Platform

“…Qiu et al, provide an overview of recent developments and applications of various types of synthetic photoswitches as molecular solar thermal (MOST) energy storage materials [11]. The application of azobenzenes performing E-Z photoisomerization upon irradiation is driven by their possible inclusion as light-triggered switches in polymers, surface-modified materials, proteins, and a variety of "molecular machines" [7,12]. Azobenzenes are highly valued photoswitches with applications in biological systems due to the fact that the photoisomerisation process is fast and they have a high photoisomerization quantum yield [2].…”