title: Effects of N-terminus modifications on the conformation and permeation activities of the synthetic peptide L1A.
abstract: We investigate the effect of the N-terminus modification of the L1A, a synthetic octadecapeptide, on its helical content, affinity and lytic action in model membranes and on its hemolytic and antibacterial activities. L1A and its acetylated analog displayed a selective antibacterial activity to Gram-negative bacteria without being hemolytic. The covalently linked 2-aminobezoic acid to the N-terminus impaired the antibacterial efficacy and increased hemolysis. Despite their lower net charge (+2), N-terminus modifications resulted in enhanced affinity and improved lytic efficiency in anionic vesicles. The analogs also showed higher helical content and consequently higher amphipathicity in these vesicles. The conformational analysis by molecular dynamics simulations in 30 % of TFE/water showed that the hydrophobic faces of the peptides are in close contact with CF3 groups of TFE while the hydrophilic faces with water molecules. Due to the loss of the amino charge, the N-termini of the analogs are buried in TFE molecules. The analysis of the pair distribution functions, obtained for the center of mass of the charged groups, has evidenced that the state of the N-terminus has influenced the possibility of different ion-pairing. The higher complexity of the bacterial cells compared with anionic vesicles hampers to establish correlations structure-function for the analogs.
authors.affiliation: Department of Physics, IBILCE, São Paulo State University, Rua Cristovão Colombo 2265, São José do Rio Preto, SP, CEP 15054-000, Brazil.
authors.forename: Luciana Puia Moro
authors.initials: LP
authors.lastname: Zanin
authors.affiliation: Department of Physics, IBILCE, São Paulo State University, Rua Cristovão Colombo 2265, São José do Rio Preto, SP, CEP 15054-000, Brazil. asaraujo@ibilce.unesp.br.
authors.forename: Alexandre Suman
authors.identifier: 0000-0001-9376-9748
authors.initials: AS
authors.lastname: de Araujo
authors.affiliation: Department of Byophysics, UNIFESP, São Paulo, Brazil.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Juliano
authors.affiliation: Department of Dermatological, Infectious and Parasitary Diseases, FAMERP, São Jose do Rio Preto, SP, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Casella
authors.affiliation: Department of Dermatological, Infectious and Parasitary Diseases, FAMERP, São Jose do Rio Preto, SP, Brazil.
authors.forename: Mara Correa Lelles
authors.initials: MC
authors.lastname: Nogueira
authors.affiliation: Department of Physics, IBILCE, São Paulo State University, Rua Cristovão Colombo 2265, São José do Rio Preto, SP, CEP 15054-000, Brazil. jruggiero@sjrp.unesp.br.
authors.forename: João
authors.initials: J
authors.lastname: Ruggiero Neto
mesh_terms: D000107:Acetylation; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000254:growth & development*; D057927:Hydrophobic and Hydrophilic Interactions; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides
keywords: Antimicrobial peptide; Biological activity; Lytic activity; Molecular dynamics; Peptide selectivity