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

Various physicochemical properties play important roles in the membrane act ivities of amphipathic antimicrobial peptides. To examine the effects of th e polar angle, two model peptides, theta rho 100 and theta rho 180, with po lar angles of 100 degrees and 180 degrees, respectively, were designed, and their interactions with membranes were investigated in detail. These pepti des have almost identical physicochemical properties except for po lar angl e. Like naturally occurring peptides, these peptides selectively bind to ac idic membranes, assuming amphipathic or-helices, and formed peptide-lipid s upramolecular complex pores accompanied by lipid flip-flop and peptide tran slocation. Despite its somewhat lower membrane affinity, theta rho 100 exhi bited 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 tra nslocation rate of theta rho 100 was higher. Furthermore, the number of pep tides 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.