The comparison of characteristics between membrane-active antifungal peptide and its pseudopeptides.
By the introduction of various amide surrogates, novel pseudopeptides corresponding to a membrane active depsipeptide were synthesized and their native characteristics compared with that of the peptide. The pseudopeptides had more resistance to serum proteases than the peptide and similar antimicrobial activities to that of the peptide without hemolytic activity. The pseudopeptides like the peptide were active against current drug resistant fungi and pathogenic fungi isolated from patients, and also had a strong synergism with current antifungal drugs against Candida albicans. The leakage assay suggested that the pseudopeptides also acted on the lipid membrane of pathogenic cells. These results indicated that the novel pseudopeptides had advantages over the peptide as a candidate for a novel antifungal drug and backbone modifications can be a tool in the development of a novel antifungal agent from membrane-active peptides isolated from natural sources or chemically synthesized.
Oh
J E
JE
Protein Chemistry Laboratory, Mogam Biotechnology Research Institute, Yongin-city, Kyunggi-Do, South Korea.
Hong
S Y
SY
Lee
K H
KH
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002942:Circular Dichroism; D047630:Depsipeptides; D004357:Drug Synergism; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D008081:Liposomes; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000494:pharmacology*
D000935:Antifungal Agents; D047630:Depsipeptides; D008081:Liposomes; D009842:Oligopeptides; C403512:lysyl-lysyl-valyl-valyl--phenylalanyl-lysyl-valyl-lysyl-phenylalanyl-lysyl-lysinamide; C119235:lysyl-lysyl-valyl-valyl-phenylalanyl-lysyl-valyl-lysyl-phenylalanyl-lysine