Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acylation
-
Anti-Infective Agents / pharmacology*
-
Chemical Phenomena
-
Chemistry, Physical
-
Endotoxins / chemistry
-
Endotoxins / metabolism
-
Escherichia coli / drug effects
-
Escherichia coli / growth & development
-
Humans
-
Lactoferrin / chemistry
-
Lactoferrin / pharmacology*
-
Lipid A / chemistry
-
Lipopolysaccharides / chemistry*
-
Peptide Fragments / chemistry
-
Peptide Fragments / pharmacology*
-
Protein Binding
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / pharmacology
-
Staphylococcus aureus / drug effects
-
Staphylococcus aureus / growth & development
-
Structure-Activity Relationship
Substances
-
Anti-Infective Agents
-
Endotoxins
-
Lipid A
-
Lipopolysaccharides
-
Peptide Fragments
-
Recombinant Proteins
-
Lactoferrin