Optical Switching of Ion−Dipole Interactions in a Gramicidin Channel Analogue

Abstract

Optical control of ion channel gating could permit the functional manipulation of excitable cells. We wished to examine the feasibility of using optical switching of ion−dipole interactions as a means of switching ion flux in channels. We prepared an analogue of the ion channel gramicidin A in which an azobenzene side chain was substituted for a valine side chain at position 1. The dipole moment of the azobenzene group can be reversibly switched between approximately 3 and 0 D by cis−trans photoisomerization. The observed conductance properties of the modified channels can be understood in terms of (switchable) ion−dipole interactions that control the height of the central barrier for Cs+ and Na+ movement through the pore. The predictable behavior of the system implies that larger dipole changes or changes closer to the central axis of the pore might effect complete gating.

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.…”

Synthesis of 3,3′-bis(sulfonato)-4,4′-bis(chloroacetamido)azobenzene and cysteine cross-linking for photo-control of protein conformation and activity

“…Examples of biomolecular systems into which azobenzene has been incorporated for photo-regulation are peptides [1][2][3] , enzymes [4][5][6][7] , oligonucleotides 8,9 and ion channels 10,11 . Methods for incorporating azobenzene chromophores into biomolecules include solid-phase peptide or oligonucleotide synthesis 7,12 , nonsense suppression via azobenzenecharged suppressor tRNAs 4 , and both non-selective 13 and targeted chemical modification of protein side chains 14 .…”

Targeted synthesis of porous aromatic frameworks with stimuli-responsive adsorption properties

“…For azobenzene, the aryl terminal distance of the non-planar cis conformation (d 4-4' ≈ 6 Å) is shorter than that of the planar trans conformation (d 4-4' ≈ 9 Å) State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012, China * Corresponding authors (emails: zhugs@jlu.edu.cn (Zhu G); renhao@jlu.edu.cn (Ren H)) [15,16]. Azobenzene trans/cis isomerization therefore results in a large change in the geometry, significantly altering the structure of the material.…”