Development of novel LL-37 derived antimicrobial peptides with LPS and LTA neutralizing and antimicrobial activities for therapeutic application.
New peptides for lipopolysaccharide (LPS) and lipoteichoic acid (LTA) neutralization in upper respiratory tract infections were developed and evaluated in terms of efficacy and safety for application in humans. Based on the sequence of the human antimicrobial peptide LL-37 we developed and investigated length variants, substitution analogues and modifications to stabilize the peptides to prevent enzymatic degradation and to improve efficacy. The most promising peptide appears P60.4, a 24 amino acid peptide with similar efficacy as LL-37 in terms of LPS and LTA neutralization and lower pro-inflammatory activity. In addition, the acetylated and amidated version of this peptide shows no toxicity and displays higher or equal antimicrobial activity compared to LL-37.
Nell
Marja J
MJ
Department of Otorhinolaryngology, Leiden University Medical Center, Leiden, The Netherlands. nell@octoplus.nl
Tjabringa
G Sandra
GS
Wafelman
Amon R
AR
Verrijk
Ruud
R
Hiemstra
Pieter S
PS
Drijfhout
Jan W
JW
Grote
Jan J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D054804:Cathelicidins; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects; D013682:Teichoic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008070:Lipopolysaccharides; D010455:Peptides; D013682:Teichoic Acids; C009900:lipoteichoic acid