Light‐Switchable Peptides with a Hemithioindigo Unit: Peptide Design, Photochromism, and Optical Spectroscopy

Abstract

This Minireview focuses on the hemithioindigo photoswitch and its use for the reversible control of three-dimensional peptide structure and related biological functions. Both the general design aspects and biophysical properties of various hemithioindigo-based chromopeptides are summarized. Hemithioindigo undergoes reversible Z→E photoisomerization after absorption of visible light. The unique ultrafast switching mechanism of hemithioindigo combines picosecond isomerization kinetics with strong double-bond torsion after light absorption, making it the ideal tool for instantaneous modulation of biological structure. Various inhibitors and model peptides based on hemithioindigo are described that can directly regulate biological signaling or allow the fastest events in peptide folding to be studied. Finally, a diverse range of chromopeptides with photoswitchable β-hairpin structures based on azobenzenes, stilbenes, and hemithioindigo are compared to emphasize the unique properties of hemithioindigo.

Picosecond Switchable Azo Dyes

“…Therefore, the corresponding molecular photoswitch should isomerize between the different states of the system as fast as possible. In fact, the development of dye molecules that exhibit fast isomerization kinetics under ambient conditions is continuing at the forefront of new research in organic chemistry, because they might open up potential applications not only within materials science but also in the biomedical field . Amongst the broad palette of molecular switches currently known, azobenzene and its substituted derivatives are the chromophores of common choice for switching applications because of their clean and highly reversible isomerization process and their ability to undergo the photoinduced trans ‐to‐ cis reaction on the subpicosecond timescale .…”

“…In fact, the development of dye moleculest hat exhibit fast isomerizationk inetics undera mbient conditions is continuing at the forefront of new research in organic chemistry,b ecause they might open up potential applications not only within materials science but also in the biomedicalf ield. [12][13][14][15][16][17][18] Amongst the broad palette of molecular switches currently known, azobenzene and its substituted derivativesa re the chromophoreso fc ommon choice for switching applications because of their clean and highly reversible isomerization process and their abilityt ou ndergo the photoinduced trans-to-cis reactiono nt he subpicosecond timescale. [19,20] The reversei somerization reactionc an be initiated thermally or by light of an appropriate wavelength.T he thermal reverse reaction in unsubstituted azobenzenes, however,i s very slow and cannotb eu sed for applications in which af ast responsei ss ought-after.T oo vercome this issue, the design and study of novel switchable azobenzene-based molecular constructs that are able to tune their opticalp roperties within the subnanosecondt emporald omain is of the essence.…”

Fulgimides as Light‐Activated Tools in Biological Investigations

“…In addition, altering the heteroaromatic moiety influences the reaction, whereby a strongly electron‐donating system lowers the reactivity , . Scheme shows the general synthesis of the thiophene fulgimide E ‐ 10 , based on a reported procedure …”

“…When compared to others, it is evident that fulgimides repre- Table 2. Photophysical properties of different photoswitches: azobenzenes, [3,37] hemithioindigos, [1,7] spiropyrans, [38][39][40][41] DASAs, [9,42,43] diarylethenes [37,[44][45][46] and fulgimides. [10,40,31] sent a promising class of photoswitches due to good thermal stability and high fatigue resistance.…”

“…[47,48] Scheme 2 shows the general synthesis of the thiophene fulgimide E-10, based on a reported procedure. [7] Due to poor yields obtained from the Stobbe condensation, improvements to the synthesis have been attempted. [22,49,50] Kiji et al reported a Pd-catalyzed carbonylation synthesis, yielding precursor fulgides and the corresponding fulgenic acids of substituted 1,4-butynediols.…”