Factors contributing to the potency of antimicrobial cationic peptides from the N-terminal region of human lactoferrin

• Published in: FEMS microbiology letters Vol. 239; no. 2; pp. 295 - 299
• Main Authors: Moriarty, Laura C., Joannou, Christopher L., van den Berg, Jeroen J.M., Gorinsky, Beatrice, Evans, Robert W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Elsevier B.V 15.10.2004; Blackwell Publishing Ltd; Blackwell; Oxford University Press
• Subjects: Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Applied microbiology; Bacteria - drug effects; Biological and medical sciences; Cationic antimicrobial peptides; Cationic peptides; Cations; Fundamental and applied biological sciences. Psychology; Glycine; Homology; Human lactoferrin peptide; Humans; Lactoferrin; Lactoferrin - chemistry; Lactoferrin - genetics; Lactoferrin - pharmacology; Microbial Sensitivity Tests; Microbiology; Peptides; Residues; Tryptophan; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Cationic antimicrobial peptides; Human lactoferrin peptide; Lactoferrin; Human; Peptides; Escherichia coli; Sequence alignment; Antimicrobial agent; Streptococcaceae; Enterococcus faecium; Bacteria; Micrococcales; Micrococcaceae; Staphylococcus aureus; Enterobacteriaceae
• ISSN: 0378-1097; 1574-6968
• DOI: 10.1016/j.femsle.2004.08.048

This study investigated the antimicrobial activities of peptides derived from the N-terminal region of human lactoferrin, and examined the contributions of individual residues to the activity of the most potent peptide. Two regions of antimicrobial activity were identified, the first corresponding to a weakly active peptide, HLP-9, comprising residues 1–9, and a second corresponding to a more potent peptide, HLP-10, comprising residues 18–26 and containing the hexapeptide motif, FQWQRN. Inhibitory studies on peptides from the first region confirm the importance of tryptophan residues in enhancing and broadening peptide activity. Inhibitory studies with glycine-substituted homologues of the more potent peptide showed that F21/G and R25/G substitutions resulted in a major reduction or complete loss of activity, while increased peptide cationicity or flexibility had little effect. Our findings demonstrate that F21 and R25 are critical determinants of potency for HLP-10, and that the second aromatic residue may act synergistically with W23 in developing and enhancing the activity of this cationic peptide.