title: Penetratin and derivatives acting as antibacterial agents.
abstract: The synthesis, in vitro evaluation and conformational study of penetratin and structurally related derivatives acting as antibacterial agents are reported. Among the compounds evaluated here, two methionine sulphoxide derivatives (RQIKIWFQNRRM[O]KWKK-NH2 and RQIKIFFQNRRM[O]KFKK-NH2 ) exhibited the strongest antibacterial effect in this series. In order to better understand the antimicrobial activity obtained for these peptides, we performed an exhaustive conformational analysis using different approaches. Molecular dynamics simulations were performed using two different media (water and trifluoroethanol/water). The results of these theoretical calculations were corroborated using experimental CD measurements. The electronic study for these peptides was carried out using molecular electrostatic potentials obtained from RHF/6-31G(d) calculations. In addition, the non-apeptide RQIRRWWQR-NH2 showed strong inhibitory action against the Gram-negative and Gram-positive bacteria tested in this study.
authors.affiliation: Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, 5700, San Luis, Argentina.
authors.forename: Adriana D
authors.initials: AD
authors.lastname: Garro
authors.forename: Mónica S
authors.initials: MS
authors.lastname: Olivella
authors.forename: José A
authors.initials: JA
authors.lastname: Bombasaro
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lima
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tapia
authors.forename: Gabriela
authors.initials: G
authors.lastname: Feresin
authors.forename: Andras
authors.initials: A
authors.lastname: Perczel
authors.forename: Csaba
authors.initials: C
authors.lastname: Somlai
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Javier
authors.initials: J
authors.lastname: López Cascales
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Enriz
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy; D002352:Carrier Proteins / Q000737:chemistry* / Q000494:pharmacology*; D057846:Cell-Penetrating Peptides; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; C414409:penetratin
keywords: antibacterial activity; conformational study; methionine sulphoxide derivatives; penetratin; small-size peptides