Enhanced antimicrobial activity of a peptide derived from human lysozyme by arylation of its tryptophan residues

Abstract

Antimicrobial peptides are valuable agents to fight antibiotic resistance. These amphipatic species display positively charged and hydrophobic amino acids. Here, we enhance the local hydrophobicity of a model peptide derived from human lysozyme (107RKWVWWRNR115) by arylation of its tryptophan (Trp) residues, which renders a positive effect on Staphylococcus aureus and Staphylococcus epidermidis growth inhibition. This site-selective modification was accessed by solid-phase peptide synthesis using the non-proteinogenic amino acid 2-aryltryptophan, generated by direct C-H activation from protected Trp. The modification brought about a relevant increase in growth inhibition: S. aureus was fully inhibited by arylation of Trp 112 and by only 10% by arylation of Trp 109 or 111, respect to the non-arylated peptide. On the other hand, S. epidermidis was fully inhibited by the three arylated peptides and the parent peptide. The minimum inhibitory concentration was significantly reduced for S. aureus depending on the arylation site.

pH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wounds

“…The minimum inhibitory concentration (MIC) of the hydrogel toward S. aureus was determined to be around 3 mg/mL (24 μM of IKFQFHFD peptide), which is comparable or superior to most of the reported antimicrobial peptides (Figure S10). , Subsequently, scanning electronic microscopy (SEM)-based bacterial morphology study and live/dead bacterial staining assay were carried out to investigate the specific mechanism behind the pH-switchable antimicrobial activity of self-assembled IKFQFHFD hydrogel. As shown in Figure b, S. aureus cells incubated with the hydrogel in pH 7.4 showed clear edges and smooth bodies.…”

Converting Teixobactin into a Cationic Antimicrobial Peptide (AMP)

“…These cationic amino acids confer aqueous solubility to the peptide and also allow for electrostatic interaction with the negatively charged bacterial cell wall, 5,6 while the hydrophobic character of the peptide facilitates interaction with the lipid bilayer membrane of bacteria. 7,8 One of the proposed mechanisms of action for cationic AMPs is inhibition of the cell wall biosynthesis via binding to lipid II, the precursor of cell wall synthesis in Gram-positive microorganisms. For example, plectasin binds to lipid II and prevents its incorporation into the peptidoglycan chain.…”

“…As such, they have a hydrophilic character as a result of the presence of a relatively high percentage of Arg and Lys residues. These cationic amino acids confer aqueous solubility to the peptide and also allow for electrostatic interaction with the negatively charged bacterial cell wall, , while the hydrophobic character of the peptide facilitates interaction with the lipid bilayer membrane of bacteria. , …”

Development of antibacterial peptides with efficient antibacterial activity, low toxicity, high membrane disruptive activity and a synergistic antibacterial effect

“…5 A large number of studies have shown that the biological activity of AMPs is closely related to the positive charge. 6 At the same time, the a-helix secondary structure also plays an important role in maintaining the bioactivity of AMPs. The amphiphilicity of AMPs is one of the important factors affecting the antibacterial activity.…”