Antimicrobial and anti-inflammatory activities of three chensinin-1 peptides containing mutation of glycine and histidine residues

Abstract

The natural peptide chensinin-1 doesnot exhibit its desired biological properties. In this study, the mutant MC1-1 was designed by replacing Gly in the chensinin-1 sequence with Trp. Mutants MC1-2 and MC1-3 were designed based on the MC1-1 sequence to investigate the specific role of His residues. The mutated peptides presented α-helicity in a membrane-mimetic environment and exhibited broad-spectrum antimicrobial activities; in contrast to Trp residues, His residues were dispensable for interacting with the cell membrane. The interactions between the mutant peptides and lipopolysaccharide (LPS) facilitated the ingestion of peptides by Gram-negative bacteria. The binding affinities of the peptides were similar, at approximately 10 μM, but ΔH for MC1-2 was −7.3 kcal.mol−1, which was 6-9 folds higher than those of MC1-1 and MC1-3, probably due to the conformational changes. All mutant peptides demonstrated the ability to inhibit LPS-induced tumour-necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release from murine RAW264.7 cells. In addition, the representative peptide MC1-1showed better inhibition of serum TNF-α and IL-6 levels compared to polymyxin B (PMB), a potent binder and neutralizer of LPS as positive control in LPS-challenged mice model. These data suggest that the mutant peptides could be promising molecules for development as chensinin-based therapeutic agents against sepsis.

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era

“…More recently, it has become evident that AMPs have a diverse range of functions in modulating immunity . The immunomodulatory properties of AMPs include reduction in the levels of proinflammatory cytokines produced in response to microbial signature molecules; modulation of the expression of chemokines; stimulation of angiogenesis; enhanced wound healing; and macrophage and leukocyte differentiation . The functions of AMPs in immune modulation are presented in Figure .…”

Antibacterial activities and molecular mechanism of amino‐terminal fragments from pig nematode antimicrobial peptide CP‐1

“…In this study, CD spectroscopy was employed to analyze the conformation of the engineered peptides in different solutions, including the aqueous and the membrane‐like environment. According to previous studies, amphiphilic AMPs usually exhibit random structure in aqueous solutions and assemble in a certain α‐helical or β‐sheet pattern when exposed to a membrane‐like environment. This conformational change, as well as transformations from the random structure to α‐helix, facilitates the engineered peptide WL3 to divide the bacterial membrane and are closely related to antimicrobial behavior …”

Development of Amphipathic Antimicrobial Peptide Foldamers Based on Magainin 2 Sequence

“…Fluorescein, encapsulated by unilamellar membrane liposomes, was prepared, as previously reported, [18][19] containing different proportions of lipids to mimic Gram-positive or Gram-negative microbial membranes. To test this, we conducted the fluorescein leakage assay to evaluate the lytic activity against microbial membrane.…”