DICARBOXYLIC-ACID ANALOGS OF GRAMICIDIN-A - DIMERIZATION KINETICS AND SINGLE CHANNEL PROPERTIES

According to the model of Urry, the cation-permeable gramicidin channel is a dimeric helix formed by association of 2 peptide monomers linked at their amino ends. Channel properties of gramicidin analogs which were obtained by chemical modification at the coupling site of the 2 half-channels are described. In these analogs the amino terminal -CHO group was replaced by -CO(CH2)n COOH (n = 2, 3, 4, 5, 6). All analogs formed conducting channels in black lipid membranes with the same general properties as found for gramicidin A. Channel-forming activity decreased with increasing pH; this was consistent with the idea that the half-channels were linked at the amino terminus. The channel lifetime of the different analogs varied between 2 ms and .gtoreq. 50 s, the longest lifetime being for the compound with n = 3. The single-channel conductance .LAMBDA. was always smaller than that of gramicidin A, but the reduction of .LAMBDA. depended on the nature of the permeable ion. Ion specificity was studied at 1 .MU. electrolyte by measuring conductance .LAMBDA. for different permeable ions (Na+, K+, Cs+). The conductance ratio .LAMBDA. (Cs+)/[I(Na+) varie between 2 and 10.5 for the different analogs.