Antimicrobial and anti-inflammatory activities of a Leu/Lys-rich antimicrobial peptide with Phe-peptoid residues.
To develop a novel cell-selective antimicrobial peptide with potent anti-inflammatory activity as well as high bacterial cell selectivity, we synthesized a Leu/Lys-rich model peptide, KLW-f (KWKKLLKKfLKLfKKLLK-NH(2)) containing two Phe-peptoid residues in its middle position. KLW-f exhibited high antimicrobial activity (the MIC range: 0.5 approximately 2.0microM) against the tested six bacterial cells. In contrast, KLW-f was no cytotoxic to human red blood cells and HeLa and NIH-3T3 cells. KLW-f caused no or little dye leakage from EYPE/EYPG (7:3, w/w) vesicles (bacterial membrane-mimicking environments), indicating its bacterial-killing action is probably not due to permeabilization/disruption of bacterial cytoplasmic membranes. Furthermore, KLW-f induced a significant inhibition in LPS-stimulated NO production from mouse macrophage RAW264.7 cells at 10microg/ml. Taken together, our results suggest that KLW-f appear to have promising therapeutic potential for future development as a novel antisepsis agent as well as antimicrobial agent.
Nan
Yong Hai
YH
Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju 501-759, Korea.
Park
Ka Hyon
KH
Jeon
Young Jin
YJ
Park
Yoonkyung
Y
Park
Il-Seon
IS
Hahm
Kyung-Soo
KS
Shin
Song Yub
SY
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000032:analysis*; D008239:Lysine / Q000032:analysis*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D034444:Peptoids / Q000737:chemistry*; D010649:Phenylalanine / Q000032:analysis*
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D005452:Fluoresceins; D010455:Peptides; D034444:Peptoids; D009569:Nitric Oxide; D010649:Phenylalanine; D007930:Leucine; D008239:Lysine; C007740:fluorexon