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 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)nCCOH (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 greater than of equal to 50 sec, the longest lifetime being found for the compound with n = 3. The single-channel conductance : formula : (see text) is always smaller than that of gramicidin A, but the reduction of : formula : (see text) depends on the nature of the permeable ion. Ion specificity was studied at 1 M electrolyte by measuring the conductance : formula : (see text) for different permeable ions (Na+, K+, Cs+). The conductance ration : formula : (see text) (Cs+)/ : formula : (see text) (Na+) was found to vary between 2 and 10.5 for the different analogs.
D055598:Chemical Phenomena; D002621:Chemistry; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004553:Electric Conductivity; D006096:Gramicidin / Q000494:pharmacology*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008081:Liposomes
D003998:Dicarboxylic Acids; D007473:Ion Channels; D008081:Liposomes; D006096:Gramicidin