Light-Switchable Hemithioindigo–Hemistilbene-Containing Peptides: Ultrafast Spectroscopy of the Z → E Isomerization of the Chromophore and the Structural Dynamics of the Peptide Moiety

Abstract

Two hemithioindigo-hemistilbene (HTI) derivatives, designed to operate as structural switches in peptides, as well as two HTI peptides are characterized by ultrafast spectroscopy in the visible and the infrared. The two HTI switches follow the reaction scheme published for other HTI compounds with a picosecond excited state reaction (τ(1) ≈ 6 ps) and isomerization from Z to E with τ(2) = 13 and 51 ps. As compared to the isolated chromophores, the isomerization reaction is slowed down in the chromopeptides to τ(2) = 24 and 69 ps. For the smaller peptide containing 6 amino acids, the structural changes of the peptide moiety observed via the IR spectrum in the amide I band follow the isomerization of the molecular switch closely. In the larger cyclic chromopeptide, containing 20 amino acids and mimicking a β-hairpin structure in the Z-form of the chromophore, the peptide moiety also changes its structure during isomerization of the chromophore. However, the IR spectrum at the end of the observation period of 3 ns deviates significantly from the stationary difference spectrum. These signatures indicate that strong additional structural changes, e.g., breaking of interchain hydrogen bonds, also occur on longer time scales.

Hemithioindigo—an emerging photoswitch

“…[57] Two HTI-containing peptides were used recently by Rück-Braun and Zinth to induce changes in peptide secondary-structures via irradiation with visible light. [58] These structural changes were monitored using ultrafast spectroscopy in the visible and the infrared region of the spectrum. The authors demonstrated that the photoisomerization of incorporated HTIs proceeds slower than the photoisomerization of the isolated HTI chromophores by a factor of 2.0 to 4.6.…”

“…This instant structural response of the peptide is followed by long term changes on the ns time scale. [58] b) HTI 26 serves as photoinducible inhibitor of the lipoxygenase LOX-12/15. While the thermodynamically stable Z isomer has only very low affinity for the enzyme, the E isomer binds strongly.…”

Hemithioindigos for Cellular Photopharmacology: Desymmetrised Molecular Switch Scaffolds Enabling Design Control over the Isomer‐Dependency of Potent Antimitotic Bioactivity

“…HTIs bear four potential substituent sites on the thioindoxyl motif and five on the hemistilbene, so we considered it potentially adapted for pharmacophore embedding in most situations where azobenzenes also succeed. Hemithioindigos oriented towards chemical biology applications (rather than in lipid physical chemistry) have mainly been employed as photoswitchable bridges or crosslinkers for conformational photoswitching of peptides; some designs for photoswitch‐appended polypeptides have also been reported . To our knowledge, only one druglike application of HTIs has been reported, where Kühn and co‐workers performed a short‐term test comparison of the HPLC‐separated E and Z isomers of a carboxylate‐bearing HTI for their capacity to inhibit oxidation of linoleic acid in human monocytes transfected to express rabbit 12/15‐lipoxygenase, with assays run over 15 min.…”

Flipping the Photoswitch: Ion Channels Under Light Control

“…Large changes in geometry and polarity, compatibility with two-photon excitation and fluorescence of the MC isomer make SPs attractive photochromes for biological applications Marriott et al 2008;Petchprayoon et al 2011). HTIs were synthesized and studied in detail recently (Figure 1c) (Cordes et al 2007;Eggers et al 2001;Herre 2005;Mostoslavskii 1970;Regner et al 2012). …”