title: Role of amphipathicity and hydrophobicity in the balance between hemolysis and peptide-membrane interactions of three related antimicrobial peptides.
abstract: Cationic antimicrobial peptides (CAMPs) represent important self defense molecules in many organisms, including humans. These peptides have a broad spectrum of activities, killing or neutralizing many Gram-negative and Gram-positive bacteria. The emergence of multidrug resistant microbes has stimulated research on the development of alternative antibiotics. In the search for new antibiotics, cationic antimicrobial peptides (CAMPs) offer a viable alternative to conventional antibiotics, as they physically disrupt the bacterial membranes, leading to lysis of microbial membranes and eventually cell death. In particular, the group of linear α-helical cationic peptides has attracted increasing interest from clinical as well as basic research during the last decade. In this work, we studied the biophysical and microbiological characteristics of three new designed CAMPs. We modified a previously studied CAMP sequence, in order to increase or diminish the hydrophobic face, changing the position of two lysines or replacing three leucines, respectively. These mutations modified the hydrophobic moment of the resulting peptides and allowed us to study the importance of this parameter in the membrane interactions of the peptides. The structural properties of the peptides were also correlated with their membrane-disruptive abilities, antimicrobial activities and hemolysis of human red blood cells.
authors.affiliation: Laboratory of Molecular Microbiology, Institute of Basic and Applied Microbiology, National University of Quilmes, Bernal, Buenos Aires, Argentina; Laboratory of Biointerfaces and Biomimetic Systems, CITSE, National University of Santiago del Estero-CONICET, Santiago del Estero, Argentina; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal.
authors.forename: Axel
authors.initials: A
authors.lastname: Hollmann
authors.affiliation: Laboratory of Molecular Microbiology, Institute of Basic and Applied Microbiology, National University of Quilmes, Bernal, Buenos Aires, Argentina.
authors.forename: Melina
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas, CONICET-University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Martín E
authors.initials: ME
authors.lastname: Noguera
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal.
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Augusto
authors.affiliation: Laboratory of Biointerfaces and Biomimetic Systems, CITSE, National University of Santiago del Estero-CONICET, Santiago del Estero, Argentina.
authors.forename: Anibal
authors.initials: A
authors.lastname: Disalvo
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal.
authors.forename: Nuno C
authors.initials: NC
authors.lastname: Santos
authors.affiliation: Laboratory of Molecular Microbiology, Institute of Basic and Applied Microbiology, National University of Quilmes, Bernal, Buenos Aires, Argentina.
authors.forename: Liliana
authors.initials: L
authors.lastname: Semorile
authors.affiliation: Laboratory of Molecular Microbiology, Institute of Basic and Applied Microbiology, National University of Quilmes, Bernal, Buenos Aires, Argentina. Electronic address: paulo.maffia@unq.edu.ar.
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Maffía
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: CAMPs; Hydrophobicity; Membrane interaction