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membrane, all peptides acquired a high amount of α-helix. The order of α-helix contentwas TOAC 13 -hy ≈ wild type peptide > TOAC 0 -hy ≥ TOAC 2 -hy.EPR assays in vesicles (Figure 2) showed that TOAC 13 -hy had the highest interactionwith both vesicle models described above. Apparently, TOAC 0 -hy had no interaction,locating outside these systems; TOAC 2 -hy is located in the interface between the vesiclesand the aqueous solution and, finally, TOAC 13 -hy is fully immersed in the membrane.These findings allowed the description of the peptide topology in the membrane, where theN-terminal region is not immersed; the position 2 is in the interface, and 13 is fullyinserted. The NLLS (Non-Linear Least-Squares simulations) in LPC indicate that, in thismimetic system interface, the TOAC 0 N-terminus has two different components. Theseresults suggest a mode of action where the N-terminal region is responsible for starting thepore formation (Figure 2B). This conclusion is in accordance with the model of poreformation to monolayer proposed by Lopes et al. [6] in Saccharomyces cerevisiae. In thismodel, the disordered peptide is attracted to the negative charged phospholipids, promotingthe formation of one amphipathic α-helix. Afterwards, the peptide remains associated withthe vesicle surface and, at the same time, the N-terminal residues are inserted among theacyl chain of the phospholipids promoting its disruption.ATOAC 0 - hyTOAC 2 - hy13TOAC - hyB3300 3320 3340 3360 3380 3400 3420Magnetic Field (G)Fig. 2. A) EPR spectra of synthetic peptides in DPPC:DPPA:DPPE (80:5:15; w:w:w); B)NLLS (Non-linear least-squares simulations) fits of the peptides in the LPC micelles. Thenoisy lines indicate the experimental results and the smoothed lines, the total NLLS fits. InTOAC 0 , the dotted lines indicate the first and second components of the system.AcknowledgmentsThis work was supported by: FAPESP, CNPq and FUNDUNESP.References1. Nakaie, C.R., Schreier, S., Paiva, A.C.M. Biochimica et Biophysica Acta 742, 63-71 (1983).2. Marchetto, R., Schreier, S., Nakaie, C.R. J. Amer. Chem. Soc. 115, 11042-11043 (1993).3. Oliveira, E., Cilli, E.M., Miranda, A., Jubilut, G.N., Albericio, F., Andreu, D., Paiva, A.C.M.,Schreier, S., Tominaga, M., Nakaie, C.R. European Journal of Organic Chemistry 21, 3686-3694(2002).4. Toniolo, C., Crisma, M., Formaggio, F. Biopolymers 47, 153-158 (1998).5. Castro, M.S., Ferreira, T.C.G., Cilli, E.M., Crusca, E., Jr., Mendes-Giannini, M.J.S., Sebben, A.,Ricart, C.A.O., Souza, M.V., Fontes, W. Peptide Science 30, 291-296 (2009).6. Lopes, J.L.S., Nobre, T.M., Siano, A., Humpola, V., Bossolan, N.R.S., Zaniquelli, M.E.D.,Tonarelli, G., Beltramini, L.M. Biochimica et Biophysica Acta 1788, 2252-2258 (2009).389