Photomodulation of ionic current through hemithioindigo-modified gramicidin channels

Abstract

Incorporation of photo-switchable amino acids into peptides and proteins offers prospects for the control of complex biochemical processes using light. Currently, only a few photo-switchable amino acids are known. We report the design and synthesis of a novel hemithioindigo-based amino acid and its incorporation into the model ion channel gramicidin. Photoisomerization of the hemithioindigo moiety between E and Z isomeric forms is shown to modulate ionic current through the channel in a predictable way. This new amino acid thus expands the possibilities for photo-control in diverse systems.

Computational prediction of ion permeation characteristics in the glycine receptor modified by photo-sensitive compounds

“…The resulting receptor would act as a logical AND circuit, with the output dependent on the presence of glycine (the sensor component) AND light, with the degree of functional control of permeation being dependent on the positioning of the photoswitch-the extreme case being an on-off switch. (Note: this distinguishes the present motif with the GA motif demonstrated earlier by Woolley and coworkers [8,9]. Their motif lacks the "second" input signal, namely gating of the channel by a chemical agonist, glycine.)…”

“…Here we address another potential design theme involving such engineered channels, namely, so as to enable the possibility for optical regulation of ion permeation characteristics. This general motif has been explored before in the context of Gramicidin A (GA) by Woolley and coworkers [8,9]. These investigators engineered optically switchable dipolar molecules on the outside of the GA pore (i.e., in the lipid bilayer membrane region, next to the pore) in such a way that when the external dipoles were switched on, the conductance of the pore was altered as a result of the change in the electrostatic forces on the permeant ions.…”

Design, Synthesis and Applications of Retinal-Based Molecular Machines

“…In fact, the analysis and modulation of the conformation and function of biomolecules (e.g. ion transport (Lougheed et al,2004), protein folding (Fierz et al, 2007), cell signalling and cell adhesion (Schütt et al, 2003) with photochromic switches is an area of increasing interest (Duvage & Demange, 2003). Among the photoisomerizable subunits for the photomodulation of secondary structure elements in peptides and proteins, photosensitive ω-amino acids are highly promising candidates.…”

Synthetic studies in sulfur heterocycles. One-pot synthesis of “thioaurones” and their conversion into [1]benzothieno[3,2-b]pyrans via tandem reactions

“…The unstable E isomer can be prepared by irradiation of the Z form with sunlight 36 or UV/VIS light. 1,[20][21][22] The equilibrium formed upon irradiation is unstable and in darkness the Z isomer is formed again. The two isomers can be distinguished based on their NMR studies.…”

“…Mention have been made of their application in photoresponsive devices and photoswitchable biomolecules. [18][19][20][21][22] Despite, the growing interest in aurones as potential medicinal agent 23 will probably result in similar interest in the thio analogs. In addition, these compounds can be used as aqueous jet-printing ink 24 and as auxiliary thermometer packaging.…”