Enhancement of antibacterial and lipopolysaccharide binding activities of a human lactoferrin peptide fragment by the addition of acyl chain.
Cationic antibacterial peptides are potentially therapeutic in the treatment of sepsis, because of their amalgamated antibacterial and lipopolysaccharide-binding activities. We prepared acyl analogues of the peptide fragment of human lactoferrin, which originally had weak antibacterial activity. It was found that 12 carbon units constitute the optimal acyl chain length, enhancing the antibacterial activity and binding of lipopolysaccharide by up to two orders of magnitude. Lactoferrin-based lipopeptides approached the activity of polymyxin B, a lipopeptide of natural origin, but were also active against Gram-positive bacteria.
Majerle
Andreja
A
Laboratory of Biotechnology, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
Kidric
Jurka
J
Jerala
Roman
R
D000215:Acylation; D000890:Anti-Infective Agents / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004731:Endotoxins / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry / Q000494:pharmacology*; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007781:Lactoferrin