Development of novel LL-37 derived antimicrobial peptides with LPS and LTA neutralizing and antimicrobial activities for therapeutic application

• Published in: Peptides (New York, N.Y. : 1980) Vol. 27; no. 4; pp. 649 - 660
• Main Authors: Nell, Marja J., Tjabringa, G. Sandra, Wafelman, Amon R., Verrijk, Ruud, Hiemstra, Pieter S., Drijfhout, Jan W., Grote, Jan J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-2006; Elsevier Science
• Subjects: Amino Acid Sequence; Animals; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Anti-Infective Agents - therapeutic use; Antimicrobial activity; Antimicrobial Cationic Peptides - chemical synthesis; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial Cationic Peptides - therapeutic use; Antimicrobial peptide; Biological and medical sciences; Cathelicidins; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Lipopolysaccharide; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - metabolism; Lipoteichoic acid; LL-37; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides - chemistry; T-Lymphocytes - drug effects; Teichoic Acids - antagonists & inhibitors; Teichoic Acids - metabolism; Upper airway infections; Vertebrates: endocrinology; Lipopolysaccharide; Upper airway infections; Antimicrobial activity; LL-37; Lipoteichoic acid; Antimicrobial peptide; Infection; Respiratory tract; Antimicrobial peptide LL-37 Lipopolysaccharide Lipoteichoic acid Antimicrobial activity Upper airway infections; Peptides; Development; Antibacterial agent; Respiratory system; Antimicrobial agent
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2005.09.016

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.