Fulgimides as Light‐Activated Tools in Biological Investigations

Abstract

With high spatiotemporal control, the conformation, rigidity and electronics of photoresponsive bioactive molecules can be altered. This, in turn, allows for control over the biological properties of these molecules. Incorporation of a photoswitchable moiety into a number of reported inhibitors, ligands and modulators has demonstrated the ability to modulate enzyme, receptor and ion channel responses using light. To date, the major classes of photoswitches explored in biological applications have been the azobenzenes and diarylethenes. Even though the use of these photoswitches has established the value of photoresponsive molecules as biological tools, several limitations have become apparent. Fulgimides represent a promising class of photoswitches that are not widely used for such biological purposes. Their properties are similar to that of diarylethenes, as their photochromism is based on a 6π‐electrocyclic rearrangement, however, fulgimides have the added advantage of thermal stability for both isomers. Fulgimides exhibit high photostationary states and fatigue resistance, with the ability to switch in aqueous buffer solutions. In this minireview, these advantageous photophysical properties will be discussed, as well as the use of fulgimides in biological investigations.

Light Regulation of Enzyme Allostery through Photo-responsive Unnatural Amino Acids

“…In the last decade, regulation of enzyme activity by light has received increasing attention in the field of synthetic biology. Various approaches have been presented, which range from the binding of light-responsive ligands at the active site to the fusion of an enzyme with a light-oxygen-voltage sensing domain (Szyma nski et al, 2013;Baker and Deiters, 2014;H€ ull et al, 2018;Losi et al, 2018;Lachmann et al, 2019;Schmermund et al, 2019). Less consideration has been dedicated to the photo-control of allosteric interactions, which are crucial regulatory features of enzymes in practically all metabolic pathways (Kastritis and Gavin, 2018).…”

Photopharmacology of Ion Channels through the Light of the Computational Microscope

“…MD simulations are expected to be particularly useful to characterize at the molecular level the effect of these novel photoswitchable molecules [ 42 , 78 , 146 , 147 ]. Although the PCLs and PTLs mentioned in this review are based on azobenzene and its trans-cis isomerization upon light irradiation, other photochromic groups are increasingly being used, such as fulgimides [ 148 ], diarylethenes [ 149 ] and stilbenes [ 150 ], for which photoswitching involves bond formation. In these cases, the aforementioned QM- and QM/MM-based approaches could be combined with docking, MD and/or excited state calculations, to model the light-induced bond formation, providing an unprecedented atomistic picture of these exciting photoswitching processes.…”

In vivo photocontrol of microtubule dynamics and integrity, migration and mitosis, by the potent GFP-imaging-compatible photoswitchable reagents SBTubA4P and SBTub2M

“…Novel photoswitches that improve practical performance are therefore gaining attention to expand the biological scope of photopharmacology. [26][27][28] To tackle these three issues in the context of microtubule photocontrol, we introduced styrylbenzothiazoles SBTub2/3 (Fig 1a) as highly metabolically stable, fully GFP/YFP/RFP-orthogonal photoswitchable tubulin inhibitors (Fig 1b-c), with excellent photoresponse to the 405 nm laser line that is standard in confocal microscopy. SBTub3 could photocontrol microtubule dynamics, organization, and MT-dependent processes in live cells with reversible temporal patterning, and with cellular and even sub-cellular spatial precision.…”