Reversible Photocontrol of Peptide Conformation with a Rhodopsin-like Photoswitch

Abstract

Reversible photocontrol of biomolecules requires chromophores that can efficiently undergo large conformational changes upon exposure to wavelengths of light that are compatible with living systems. We designed a benzylidene-pyrroline chromophore that mimics the Schiff base of rhodopsin and can be used to introduce light-switchable intramolecular cross-links in peptides and proteins. This new class of photoswitch undergoes an ~10 Å change in end-to-end distance upon isomerization and can be used to control the conformation of a target peptide efficiently and reversibly using, alternately, violet (400 nm) and blue (446 nm) light.

Synthesis and Photoisomerization of Rhodopsin‐Based Molecular Switches

“…[16] The E isomer of switches 5 is expected to be more stable than the Z isomer owing to steric repulsion between substit-uents R 1 and R 2 . We also checked the use of ketones with the aim Scheme 1.…”

Photochromic Materials in Biochemistry

“…Several studies have been conducted on smaller peptide sequences and simpler elements of protein secondary structure, such as α-helices and β-hairpins, using photoswitchable cross-linked groups [9,12,[54][55][56][57][58][59][60][61][62][63][64][65]. The structural distortion can often be predicted to some degree by comparing the distance between the attachment points in the peptide and the distance between the linkage sites on the chromophore [61,66].…”

Visible light sensitized isomerization of rhodopsin-based molecular switches

“…Although any of these alternatives enable the use of visible light compatible with biological systems, all of them require the modification of the chromophore by designing a specific synthetic route (substituent effect) or altering the reaction conditions (Lewis acids). For the rhodopsin-based switches, 8 these conditions include water as solvent at pH = 5. This prevents the use of these switches with acid-labile substrates and, more importantly, in organic solvents.…”

“…This result greatly increases the applicability of these systems beyond the excellent photophysical properties as photoswitches already reported. 8,14,15 The triplet state of 1 was also studied by laser flash photolysis. The triplet state decay of a solution of xanthone in acetonitrile was measured.…”

“…14,15 Additionally, they have been used to control the conformation of a peptide. 8 First, we tested the sensitized photochemistry of 1. To do this, we used thioxanthone as a triplet sensitizer (E T = 63.2 kcal/mol).…”