Bulky aromatic amino acids increase the antibacterial activity of 15-residue bovine lactoferricin derivatives

A model peptide, FKCRRWQWRMKKLGA, residues 17-31 of bovine lactoferricin, h as been subjected to structure-antibacterial activity relationship studies. The two Trp residues are very important for antibacterial activity, and an alogue studies have demonstrated the significance of the size, shape and ar omatic character of the side chains. In the current study we have replaced Trp residues in the model peptide with bulky aromatic amino acids to elucid ate further the importance of size and shape. The counterproductive Cys res idue in position 3 was also replaced by these aromatic amino acids. The lar gest aromatic amino acids employed resulted in the most active peptides. Th e peptides containing these hydrophobic residues were generally more active against Staphylococcus aureus than against Escherichia coli, indicating th at the bacterial specificity as well as the antibacterial efficiency can be altered by employing large hydrophobic aromatic amino acid residues. Copyr ight (C) 2001 European Peptide Society and John Wiley & Sons, Ltd.