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

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. Observing rapid changes: Hemithioindigos (HTIs) are promising photoswitchable tools for various applications. The design, applications, biophysical studies, and ultrafast spectroscopy of HTI amino acid building blocks and peptides with picosecond isomerization dynamics are reviewed. Photoresponsive chromopeptides allow structural transitions in the secondary structure of peptides to be monitored in time regimes down to nanoseconds (see figure).