Penetratin and derivatives acting as antibacterial agents

ADRIANA GARRO; MONICA OLIVELLA; JOSE BOMBASARO; BEATRIZ LIMA; ALEJANDRO TAPIA; GABRIELA EGLY FERESIN; ANDRAS PERCZEL; CSABA SOMLAI ; BOTOND PENKE ; JAVIER LOPEZ CASCALES ; ANA MARIA RODRIGUEZ; DANIEL ENRIZ

CHEMICAL BIOLOGY & DRUG DESIGN

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2013 vol. 82 p. 167 - 177

1747-0277

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.