Abstract
A series of helical structures for gramicidin A, with alternating L and D residues, are characterized as to number of residues per turn, atoms in hydrogenbonded rings, and dihedral angles. Because of alternating peptide C-O directions, these helices are capable of forming head-to-head hydrogen-bonded dimers with the capacity of functioning as transmembrane channels. The dimers are characterized as to channel length, pore size, and expected ion selectivity. In a test of the proposed head-to-head association for channel formation, the malonyl dimer [N,N'-(dideformyl gramicidin A)-malonamide] was synthesized. The chemical and conformational integrity of the product was verified by nuclear magnetic resonance; in lipid bilayer studies, the dimer was found to be a potent mediator of ion conductance with the predicted concentration dependence.Thus, the results on malonyl gramicidin A prove head-to-head association in formation of the transmembrane channel, and the results are consistent with the specific geometrical configuration involved in head-to-head dimerization of pi((L,D)) helices. At this stage, the action of gramicidin A on membranes with lipid-layer thicknesses of 30 A or less can best be understood in terms of the pi((L,D)) helix with 6.3 residues per turn.