De novo designed cyclic cationic peptides as inhibitors of plant pathogenic bacteria.
Head-to-tail cyclic peptides of 4-10 residues consisting of alternating hydrophilic (Lys) and hydrophobic (Leu and Phe) amino acids were synthesized and tested against the economically important plant pathogenic bacteria Erwinia amylovora, Xanthomonas vesicatoria and Pseudomonas syringae. The antibacterial activity, evaluated as the minimal inhibitory concentration (MIC), the cytotoxicity against human red blood cells and stability towards protease degradation were determined. The influence of cyclization, ring size, and replacement of l-Phe with d-Phe on antibacterial and hemolytic activities was studied and correlated with the degree of structuring and hydrophobicity. Our results showed that linear peptides were inactive against the three bacteria tested. Cyclic peptides were active only toward X. vesicatoria and P. syringae, being c(KLKLKFKLKQ) (BPC10L) the most active peptide with MIC values of 6.25 and 12.5 microM, respectively. The improved antibacterial activity of cyclic peptides compared to their linear counterparts was associated to an increase of the hydrophobicity, represented as RP-HPLC retention time (t(R)), and secondary structure content which are related to an enhanced amphipathicity. A decrease of antibacterial and hemolytic activities was observed when a d-Phe was introduced into the cyclic sequences, which was attributed to their low amphipathicity as shown by their low secondary structure content and low t(R). The small size, simple structure, bactericidal effect, and stability to protease degradation of the best peptides make them potential candidates for the development of effective antibacterial agents for use in plant protection.
Monroc
Sylvie
S
Laboratori d'Innovació en Processos i Productes de Síntesi Orgànica (LIPPSO), Departament de Química, Universitat de Girona, Campus Montilivi, 17071 Girona, Spain.
Badosa
Esther
E
Feliu
Lidia
L
Planas
Marta
M
Montesinos
Emili
E
Bardají
Eduard
E
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D003500:Cyclization; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D010935:Plant Diseases / Q000382:microbiology; D010944:Plants
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010456:Peptides, Cyclic