10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities

Abstract

Natural antimicrobial peptides (AMPs) are multifunctional host defense peptides (HDPs) that are valuable for various therapeutic applications. In particular, natural and artificial AMPs with dual antibacterial immunomodulatory functions emerged as promising candidates for the development of therapeutic agents to treat infectious inflammation. In an effort to develop useful AMP variants with short lengths and simple amino acid composition, we devised a de novo design strategy to generate a series of model peptide isomer sequences, named WALK peptides, i.e., tryptophan (W)-containing amphipathic-helical (A) leucine (L)/lysine (K) peptides. Here, we generated two groups of WALK peptide isomers: W2L4K4 (WALK244.01~WALK244.10) and W2L4K3 (WALK243.01~WALK243.09). Most showed apparent antibacterial activities against both Gram-positive and Gram-negative bacteria at a concentration of approximately 4 μg/mL along with varied hemolytic activities against human red blood cells. In addition, some exhibited significant anti-inflammatory activities without any significant cytotoxicity in macrophages. Collectively, these results suggest that the two selected peptides, WALK244.04 and WALK243.04, showed promise for the development of antibacterial and anti-inflammatory agents.

Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

“…This peptide was strategically designed with a focus on WALK, an acronym signifying tryptophan-containing amphipathic-helical leucine/lysine peptides. These peptides emulate the cationic, amphipathic α-helical structures found in antimicrobial peptides, utilizing only three types of amino acids [ 31 ]. In our study, WALK244.04 was used as the positive control and underwent molecular docking simulations as the ligand for the TLR4/MD2 receptor.…”

“…The WALK244.04 peptide, an experimentally validated AMP, was employed as the positive control for the validation of both the universal adjuvant (MRh4-679) and anticancer (SBsib-711) peptides, as they all complexed with same receptor, TLR4/MD2. WALK244.04 has shown an MIC (minimum inhibitory concentration) value of approximately 4.0–8.0 µg/mL against Gram-positive ( Bacillus subtilis and Staphylococcus aureus ) and Gram-negative bacteria ( Escherichia coli and Shigella dysentariae ) [ 31 ]. The parallel performances of docking and MD simulation studies for WALK244.04, as a confirmed ligand of TLR4, with the identified TLR ligands in this study reconfirm the utility of the novel candidates for further trials.…”

The Contribution of Antimicrobial Peptides to Immune Cell Function: A Review of Recent Advances

“…In 2022, Kim et al constructed two sets of WALK peptide isomers, WALK244.01-WALK244.10 and WALK243.01-WALK243.09. The peptides were shown to inhibit the TRIF-dependent signaling pathway in macrophages and production of iNOS, COX-2, and IL-1β [ 109 ]. Moreover, some AMPs used as feed additives significantly increase the phagocytosis rate and phagocytic index of RAW264.7 cells against chicken erythrocytes and enhance the nonspecific immune function of mice [ 120 ].…”