title: Small Peptides Derived from Penetratin as Antibacterial Agents.
abstract: The synthesis, in vitro evaluation and conformational study of several small-size peptides acting as antibacterial agents are reported. Among the compounds evaluated, the peptides Arg-Gln-Ile-Lys-Ile-Trp-Arg-Arg-Met-Lys-Trp-Lys-Lys-NH2 , Arg-Gln-Ile-Lys-Ile-Arg-Arg-Met-Lys-Trp-Arg-NH2 , and Arg-Gln-Ile-Trp-Trp-Trp-Trp-Gln-Arg-NH2 exhibited significant antibacterial activity. These were found to be very active antibacterial compounds, considering their small molecular size. In order to better understand the antibacterial activity obtained for these peptides, an exhaustive conformational analysis was performed, using both theoretical calculations and experimental measurements. Molecular dynamics simulations using two different media (water and trifluoroethanol/water) were employed. The results of these theoretical calculations were corroborated by experimental circular dichroism measurements. A brief discussion on the possible mechanism of action of these peptides at molecular level is also presented. Some of the peptides reported here constitute very interesting structures to be used as starting compounds for the design of new small-size peptides possessing antibacterial activity.
authors.affiliation: Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.|IMIBIO-SL, CONICET, San Luis, Argentina.|Instituto de Química Orgánica, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, San Miguel de Tucumán, Argentina.
authors.forename: Oscar
authors.initials: O
authors.lastname: Parravicini
authors.affiliation: Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Somlai
authors.affiliation: Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.|IMIBIO-SL, CONICET, San Luis, Argentina.
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Andujar
authors.affiliation: Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.|IMASL, CONICET, San Luis, Argentina.
authors.forename: Adriana D
authors.initials: AD
authors.lastname: Garro
authors.affiliation: Instituto de Biotecnología, Instituto de Ciencias Básicas, Universidad Nacional de San Juan, San Juan, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lima
authors.affiliation: Instituto de Biotecnología, Instituto de Ciencias Básicas, Universidad Nacional de San Juan, San Juan, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tapia
authors.affiliation: Instituto de Biotecnología, Instituto de Ciencias Básicas, Universidad Nacional de San Juan, San Juan, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Feresin
authors.affiliation: MTA-ELTE Protein Modelling Research Group, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Andras
authors.initials: A
authors.lastname: Perczel
authors.affiliation: Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Tóth
authors.affiliation: Grupo de Bioinformática y Macromoléculas (BioMac) Aulario II, Universidad Politécnica de Cartagena, Cartagena, Murcia, Spain.
authors.forename: Javier López
authors.initials: JL
authors.lastname: Cascales
authors.affiliation: Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.|IMIBIO-SL, CONICET, San Luis, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez
authors.affiliation: Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.|IMIBIO-SL, CONICET, San Luis, Argentina.
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Enriz
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry*; D057846:Cell-Penetrating Peptides; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D012475:Salmonella / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; C414409:penetratin
keywords: Antibacterial activity; Peptide syntheses; Rational drug design