The role of tryptophan in the antibacterial activity of a 15-residue bovine lactoferricin peptide

Bovine lactoferricin is a 25-residue antibacterial peptide isolated after g astric cleavage of the iron transporting protein lactoferrin. A 15-residue fragment, FKCRRWQWRMKKLGA of this peptide sustains most of the antibacteria l activity. In this truncated sequence, the two Trp residues are found to b e essential for antibacterial activity. The anchoring properties of Trp, as have been observed in membrane proteins, are believed to be important for the interaction of Trp containing antibacterial peptides with bacterial cel l membranes. We have investigated the molecular properties which make Trp i mportant for the antibacterial activity of the 15-residue peptide by replac ing Trp with natural and unnatural aromatic amino acids. This series of pep tides was tested for antibacterial activity against Echerichia coli and Sta phylococcus aurcus. We found that neither the hydrogen bonding ability nor the amphipathicity of the indole system are essential properties for the ef fect of Trp on the antibacterial activity of the peptides, Replacement of T rp with residues containing aromatic hydrocarbon side chains gave the most active peptides. We propose that aromatic hydrocarbon residues are able to position themselves deeper into the bacterial cell membrane, making the pep tide more efficient in disrupting the bacterial cell membrane. From our res ults the size, shape and aromatic character of Trp seem to be the most impo rtant features for the activity of this class of Trp containing antibacteri al peptides. Copyright (C) 2001 European Peptide Society and John Wiley Br Sons, Ltd.