Penetratin and Derivatives Acting as Antibacterial Agents

• Published in: Chemical biology & drug design 2013-08, Vol.82 (2), p.167-177
• Main Authors: Garro, Adriana D., Olivella, Mónica S., Bombasaro, José A., Lima, Beatriz, Tapia, Alejandro, Feresin, Gabriela, Perczel, Andras, Somlai, Csaba, Penke, Botond, López Cascales, Javier, Rodríguez, Ana M., Enriz, Ricardo D.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial activity; Bacterial Infections - drug therapy; Carrier Proteins - chemistry; Carrier Proteins - pharmacology; conformational study; Humans; methionine sulphoxide derivatives; Models, Molecular; Molecular Sequence Data; penetratin; Protein Conformation; small-size peptides
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12143

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. In this study we report the synthesis, in vitro evaluation, and conformational study of penetratin and structurally related derivatives acting as antibacterial agents. Among the compounds evaluated two methionine sulfoxide derivatives (RQIKIWFQNRRM[O] KWKK‐NH2 and RQIKIFFQNRRM[O]KFKK‐NH2) and a nonapeptide (RQIRRWWQR‐NH2) exhibited the strongest antibacterial effect against the Gram‐negative and Gram‐positive bacteria tested in this study.