Open AccessFactors contributing to the potency of antimicrobial cationic peptides from the N‐terminal region of human lactoferrin
Author(s) -
Moriarty Laura C.,
Joannou Christopher L.,
Berg Jeroen J.M.,
Gorinsky Beatrice,
Evans Robert W.
Publication year - 2004
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1016/j.femsle.2004.08.048
Subject(s) - lactoferrin , peptide , antimicrobial , chemistry , residue (chemistry) , potency , biochemistry , tryptophan , peptide sequence , structure–activity relationship , antimicrobial peptides , cathelicidin , cationic polymerization , amino acid , stereochemistry , in vitro , gene , organic chemistry
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.