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Updated: Jun 23, 2026

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
Published on: July 4, 2016
Molecular recognition and self-assembly special feature: Calix[4]arene-based conical-shaped ligands for
Vera Martos1, Sarah C Bell, Eva Santos
1Institute of Chemical Research of Catalonia, Avinguda Països Catalans 16, 43007 Tarragona, Spain.
Abstract:
Potassium channels are among the core functional elements of life because they underpin essential cellular functions including excitability, homeostasis, and secretion. We present here a series of multivalent calix[4]arene ligands that bind to the surface of voltage-dependent potassium channels (K(v)1.x) in a reversible manner. Molecular modeling correctly predicts the best candidates with a conical C(4) symmetry for optimal binding, and the effects on channel function are assessed electrophysiologically. Reversible inhibition was observed, without noticeable damage of the oocytes, for tetraacylguanidinium or tetraarginine members of the series with small lower rim O-substituents. Apparent binding constants were in the low micromolar range and had Hill coefficients of 1, consistent with a single site of binding. Suppression of current amplitude was accompanied by a positive shift in the voltage dependence of gating and slowing of both voltage sensor motion and channel opening. These effects are in keeping with expectations for docking in the central pore and interaction with the pore domain "turret."
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