Penetratin and derivatives acting as antibacterial agents.

ADRIANA D. GARRO; MÓNICA S. OLIVELLA; JOSÉ A. BOMBASARO; BEATRIZ LIMA; ALEJANDRO TAPIA; GABRIELA FERESIN; ANDRAS PERCZEL; CSABA SOMLAI; BOTOND PENKE; JAVIER LÓPEZ CASCALES; ANA M. RODRÍGUEZ; RICARDO D. ENRIZ

Chemical Biology & Drug Design

wiley

Año: 2013

1747-0285

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 sulfoxide 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 TFE/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 nonapeptide RQIRRWWQR-NH2 showed strong inhibitory action against the Gram-negative and Gram-positive bacteria tested in this study.