Voltage-dependent ion channels formed by dodeca- and pentadecaoligopeptides with two charged terminal groups

Abstract

Two voltage-dependent ion channels composed of dodeca- and pentadecaoligopeptides, NH 3 +- l-Ala- d-Leu- l-Ala- d-Val- l-Val- d-Val- l-Trp- d-Leu- l-Trp- d-Leu- l-Trp- d-Leu-CO 2 − ( 3) and NH 3 +- l-Val-Gly- l-Ala- d-Leu- l-Ala- d-Val- l-Val- d-Val- l-Trp- d-Leu- l-Trp- d-Leu- l-Trp- d-Leu- l-Trp-CO 2 − ( 4), were synthesized. Both oligopeptides have charged species asymmetrically located at the N- and C-terminals. When dodecapeptide 3 was incorporated into planar bilayer membranes and voltage was applied in the range +200 to −200 mV under symmetric 500 mM KCl conditions, stable single ion channel currents were observed. The open probability of these single ion channels was dependent on the applied voltage, and higher open probabilities were observed either at high positive or negative applied voltages, with the voltage-dependence of the open probability being almost randomly distributed. The current–voltage relationship for 3 was ohmic and channel conductances were in the range 5.2–11.2 pS under the same salt conditions. On the other hand, pentadecapeptide 4 showed multi-channel activity with voltage dependency, i.e., the magnitude of the whole currents per unit time was dependent on the applied voltage. For large applied voltage steps, large amplitude whole channel currents were observed. Based on comparisons of the behaviors of various lengths of oligopeptides, extended structures through the lipid membrane of 3 and 4 were proposed as the active forms of the ion channel species.