| Autor: |
Chiarpotti MV; Instituto Interdisciplinario de Ciencias Básicas (ICB)─CONICET/UNCUYO. Padre Jorge Contreras 1300, CP 5500 Mendoza, Argentina.; Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Padre Jorge Contreras 1300, CP 5500 Mendoza, Argentina.; AI Proteins, 20 Overland Street, Boston, Massachusetts 02215, United States., Galassi VV; Instituto Interdisciplinario de Ciencias Básicas (ICB)─CONICET/UNCUYO. Padre Jorge Contreras 1300, CP 5500 Mendoza, Argentina.; Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Padre Jorge Contreras 1300, CP 5500 Mendoza, Argentina., Longo GS; Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), UNLP-CONICET, Diagonal 113 & 64 S/N, CP B1904DPI La Plata, Argentina., Del Pópolo MG; Instituto Interdisciplinario de Ciencias Básicas (ICB)─CONICET/UNCUYO. Padre Jorge Contreras 1300, CP 5500 Mendoza, Argentina.; Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Padre Jorge Contreras 1300, CP 5500 Mendoza, Argentina. |
| Abstrakt: |
pH-sensitive peptides bind and traverse lipid membranes in response to changes in pH. They can be used to target tumors and other acidic tissues. We investigate the influence of acidic lipids on the pH-driven adsorption of recently synthesized peptides. Using a statistical-thermodynamic theory that takes into account the acid-base chemistry of peptides and lipids, we find that the presence of acidic lipids amplifies changes in peptide surface concentration when transitioning from high to low pH. We study cyclic and linear peptides, containing tryptophan, glutamic acid, and arginine residues, examining their behavior in both neutral and acidic membranes. Membrane binding consistently results from the shallow insertion of tryptophan residues with hydrophilic residues facing the aqueous solution. Regardless of the pH, the peptide's geometry predominantly determines the orientation and distribution of residues. Notably, we find that not only the extent of adsorption is pH-sensitive but also the underlying adsorption mechanism: it is barrier-free at low pH but hindered by a large free energy barrier at high pH. Hence, under more acidic conditions, pH-sensitive peptides show facilitated adsorption both kinetically and thermodynamically. |
