Role of tryptophan residues in antimicrobial activity and membrane interactions

Antimicrobial peptides are heavily modified by inclusion of non-native amino acids, peptide cyclization and addition of nonpeptide moieties such as carbohydrates or fatty acids. Peptide acylation can significantly improve the antimicrobial potency of antimicrobial peptides, which primarily target the microbial membrane. This type of antimicrobi-als, which do not target a specific receptor and whose activity is based on the characteristic lipid composition of microbial membrane has the advantage that it takes microorganism several hundred generations at low concentrations of amphipathic antimicrobial peptide to achieve resistance. In particular, tryptophan and arginine residues have been shown to be almost indispensable due to their amphipathic and cationic character. For instance, arenicin-1, indolicidin, tritrpticin, pleurocidin, melittin, cecropin and so on are having these characteristics. And it also seems to be related to interaction ability in microbial phospholipid membranes. Tryptophan was the first enzyme for which a product formed at one site was demon-strated to be intramolecularly transferred to another site, contributing to substrate channeling. In the history of enzymology and structural biology, tryptophan residue has served a key role because its spatial and functional relationship was deeply investigated. The distinguishing structural characteristic of tryptophan is that it contains an indole functional group. Interestingly, some of antimicrobial peptide showed that tryptophan plays a pivotal role in the membrane-directed antimicrobial activity. The hydrophobic tryptophan residue may support a more efficient interaction with the fungal membrane and bacterial membrane surfaces allowing the peptides to partition into the bilayer interface, in contrast with other hydrophobic residues. Furthermore, chemicals involved indole functional group also possessed membrane interaction ability with antimicrobial effects.