Dicarboxylic acid analogs of Gramicidin A: Dimerization kinetics and single channel properties

Abstract

According to the model of Urry, the cation-permeable gramicidin channel is a dimeric helix formed by association of two peptide monomers linked at their amino ends. In this paper the channel properties of gramicidin analogs are described which have been obtained by chemical modification at the coupling site of the two half-channels. In these analogs the amino terminal-CHO group is replaced by-CO(CH₂) _n COOH(n=2, 3, 4, 5, 6). All analogs form conducting channels in black lipid membranes with the same general properties as found for gramicidin A. The observation that the channel-forming activity decreases with increasing pH is consistent with the notion that the half-channels are linked at the amino terminus. The channel lifetime of the different analogs varies between 2 msec and ≧50 sec, the longest lifetime being found for the compound withn=3. The single-channel conductance Λ is always smaller than that of gramicidin A, but the reduction of Λ depends on the nature of the permeable ion. Ion specificity was studied at 1m electrolyte by measuring the conductance Λ for different permeable ions (Na⁺, K⁺, Cs⁺). The conductance ratio^Λ(Cs⁺)/^Λ(Na⁺) was found to vary between 2 and 10.5 for the different analogs.