Antimicrobial activity of short arginine‐ and tryptophan‐rich peptides

Abstract

Highly antimicrobial active arginine- and tryptophan-rich peptides were synthesized ranging in size from 11 to five amino acid residues in order to elucidate the main structural requirement for such short antimicrobial peptides. The amino acid sequences of the peptides were based on previous studies of longer bovine and murine lactoferricin derivatives. Most of the peptides showed strong inhibitory action against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive bacterium Staphylococcus aureus. For the most active derivatives, the minimal inhibitory concentration values observed for the Gram-negative bacteria were 5 microg/ml (3.5 microM), whereas it was 2.5 microg/ml (1.5 microM) for the Gram-positive bacterium. It was essential for the antimicrobial activity that the peptides contained a minimum of three tryptophan and three arginine residues, and carried a free N-terminal amino group and an amidated C-terminal end. Furthermore, a minimum sequence size of seven amino acid residues was required for a high antimicrobial activity against Pseudomonas aeruginosa. The insertion of additional arginine and tryptophan residues into the peptides resulted only in small variations in the antimicrobial activity, whereas replacement of a tryptophan residue with tyrosine in the hepta- and hexapeptides resulted in reduced antimicrobial activity, especially against the Gram-negative bacteria. The peptides were non-haemolytic, making them highly potent as prospective antibiotic agents.

Variations in Amino Acid Composition of Antisense Peptide-Phosphorodiamidate Morpholino Oligomer Affect Potency against Escherichia coli In Vitro and In Vivo

“…Because 6-aminohexanoic acid has no side chain, the presumed interaction with the hydrophobic core of the bilayer may be quite different from that of phenylalanine. Previous results have concluded that for short membrane-penetrating peptides (such as the ones that we used), the composition of the amino acids is more important than the order of the amino acids (19,20).…”

Conformation of a Bactericidal Domain of Puroindoline a: Structure and Mechanism of Action of a 13-Residue Antimicrobial Peptide

“…Trp-rich cationic antimicrobial peptides have recently attracted increased interest from researchers because Trp residues are known to play important roles in the antimicrobial and hemolytic activities of antimicrobial peptides (14,23,48,54,56,57). A well-studied representative of the group of Trp-rich antimicrobial peptides is indolicidin.…”

Length Effects in Antimicrobial Peptides of the (RW)nSeries

“…Truncated peptide sequences from indolicidin and lactoferricin with conserved RW motifs retain antimicrobial activity even when their original secondary structure is lost (45,53), suggesting that R and W content alone correlates with activity. QSAR analysis of the antimicrobial activities of R and W peptides suggests that charge and multiple W side chains are necessary, while W can be replaced by analogs with bulkier side chains (24,46,48). The results also suggest that, in short peptides, the order of amino acids is less important than the overall composition with respect to cationic and lipophilic residues (41,46,47).…”