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

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 therapeu...

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Published in:Antibiotics (Basel) 2022-11, Vol.11 (11), p.1588
Main Authors: Kim, Su-Jin, Kang, Tae-Bong, Kim, Dong-Hyuk, Keum, Minho, Lee, Sung-Hee, Kim, Ji-Hun, Lee, Sang-Hyuck, Kim, Jihoon, Kweon, Hyuk-Jung, Park, Jae-Won, Kim, Beom-Jun, Won, Hyung-Sik
Format: Article
Language:English
Subjects:
Amino acid composition
Amino acids
anti-inflammatory activity
Anti-inflammatory agents
Anti-inflammatory drugs
Antibacterial activity
Antibacterial agents
Antibiotics
Antimicrobial peptides
Bacteria
Chemical compounds
Cytotoxicity
de novo design
Design
Drug resistance
Erythrocytes
Gram-negative bacteria
Gram-positive bacteria
host defense peptides
Immunomodulation
Inflammation
Isomers
Leucine
Lysine
Macrophages
Pathogens
Peptides
Pharmacology
Sequences
Spectrum analysis
Therapeutic applications
Toxicity
Tryptophan
WALK peptides
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Summary: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.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics11111588