Polar angle as a determinant of amphipathic α-helix-lipid interactions:: A model peptide study

Various physicochemical properties play important roles in the membrane activities of amphipathic antimicrobial peptides. To examine the effects of the polar angle, two model peptides, theta rho 100 and theta rho 180, with polar angles of 100 degrees and 180 degrees, respectively, were designed, and their interactions with membranes were investigated in detail. These peptides have almost identical physicochemical properties except for po lar angle. Like naturally occurring peptides, these peptides selectively bind to acidic membranes, assuming amphipathic or-helices, and formed peptide-lipid supramolecular complex pores accompanied by lipid flip-flop and peptide translocation. Despite its somewhat lower membrane affinity, theta rho 100 exhibited higher membrane permeabilization activity, a greater flip-flop rate, as well as more antimicrobial activity due to a higher pore formation rate compared with theta rho 180. Consistent with these results, the peptide translocation rate of theta rho 100 was higher. Furthermore, the number of peptides constituting theta rho 100 pores was less than that of theta rho 180, and theta rho 100 pores involved more lipid molecules, as reflected by its cation selectivity. The polar angle was found to be an important parameter determining peptide-lipid interactions.