Structure-activity analysis and biological studies of chensinin-1b analogues

Dong, Weibing; Dong, Zhe; Mao, Xiaoman; Sun, Yue; Li, Fēi; Shang, Dejing

doi:10.1016/j.actbio.2016.04.003

Cited by 12 publications

(5 citation statements)

References 33 publications

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“…The MIC assay performed indicated the truncated peptides are less effective as antimicrobial agent compared to the full-length sequence, which is consistent with recent reports in literature [61,62,63]. However, antimicrobial activity for AMPs is not exclusively linked to peptide length, as many naturally occurring AMPs are as short as the shortest sequences tested here [64,65].…”

Section: Discussionsupporting

confidence: 91%

Characterization and Antimicrobial Activity of Amphiphilic Peptide AP3 and Derivative Sequences

2019

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The continued emergence of new antibiotic resistant bacterial strains has resulted in great interest in the development of new antimicrobial treatments. Antimicrobial peptides (AMPs) are one of many potential classes of molecules to help meet this emerging need. AMPs are naturally derived sequences, which act as part of the innate immune system of organisms ranging from insects through humans. We investigated the antimicrobial peptide AP3, which is originally isolated from the winter flounder Pleuronectes americanus. This peptide is of specific interest because it does not exhibit the canonical facially amphiphilic orientation of side chains when in a helical orientation. Different analogs of AP3 were synthesized in which length, charge identity, and Trp position were varied to investigate the sequence-structure and activity relationship. We performed biophysical and microbiological characterization using fluorescence spectroscopy, CD spectroscopy, vesicle leakage assays, bacterial membrane permeabilization assays, and minimal inhibitory concentration (MIC) assays. Fluorescence spectroscopy showed that the peptides bind to lipid bilayers to similar extents, while CD spectra show the peptides adopt helical conformations. All five peptides tested in this study exhibited binding to model lipid membranes, while the truncated peptides showed no measurable antimicrobial activity. The most active peptide proved to be the parent peptide AP3 with the highest degree of leakage and bacterial membrane permeabilization. Moreover, it was found that the ability to permeabilize model and bacterial membranes correlated most closely with the ability to predict antimicrobial activity.

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Section: Discussionsupporting

confidence: 91%

Characterization and Antimicrobial Activity of Amphiphilic Peptide AP3 and Derivative Sequences

2019

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“…However, the results revealed a reduction in antimicrobial potency. Hence, to identify if the C-terminus of GL-22 was important, several analogues, LF-10 (LFVNVLDKIR-NH 2 ), FV-9 (FVNVLDKIR-NH 2 ), VN-8 (VNVLDKIR-NH 2 ) and FV-8 (FVNVLDKI-NH 2 ), were designed to determine which region was important for the potency of these peptides [ 25 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…However, a shorter peptide, with only eight residues from the temporin family, was reported to have high potency against Gram-positive bacteria [ 20 ]. For example, peptides truncated from chensinin-1b, as short as nine residues, also possess some activity against both Gram-positive and Gram-negative bacteria [ 33 ], suggesting that the loss of bioactivity was not completely related to the short length. Additionally, cationic residues are of great importance as the electrostatic interaction between positively charged amino acids and the anionic components (e.g., membrane lipids) of cell surfaces lead to the initial attraction of AMPs to the pathogen cell surface [ 41 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Targeted Modification and Structure-Activity Study of GL-29, an Analogue of the Antimicrobial Peptide Palustrin-2ISb

et al. 2022

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Antimicrobial peptides (AMPs) are considered as promising antimicrobial agents due to their potent bioactivity. Palustrin-2 peptides were previously found to exhibit broad-spectrum antimicrobial activity with low haemolytic activity. Therefore, GL-29 was used as a template for further modification and study. Firstly, the truncated analogue, GL-22, was designed to examine the function of the ‘Rana box’, which was confirmed to have no impact on antimicrobial activity. The results of antimicrobial activity assessment against seven microorganisms demonstrated GL-22 to have a broad-spectrum antimicrobial activity, but weak potency against Candida albicans (C. albicans). These data were similar to those of GL-29, but GL-22 showed much lower haemolysis and lower cytotoxicity against HaCaT cells. Moreover, GL-22 exhibited potent in vivo activity at 4 × MIC against Staphylococcus aureus (S. aureus)-infected larvae. Several short analogues, from the C-terminus and N-terminus of GL-22, were modified to identify the shortest functional motif. However, the results demonstrated that the shorter peptides did not exhibit potent antimicrobial activity, and the factors that affect the bioactive potency of these short analogues need to be further studied.

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“…Chensinin-1b is a synthetic derivative of native AMP originally identified from Rana chensinensis, with a broader spectrum and enhanced antimicrobial properties [54][55][56]. Additionally, we have previously demonstrated that chensinin-1b improves tissue repair and sepsis outcomes in wound infection and sepsis models [67,68], indicating a potential function in the repolarization of macrophages. Therefore, we focused on the possible role of chensinin-1b in repolarizing macrophages and treating inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Antibiotic administration and fecal microbiota transplantation have beneficial effects on colonic inflammation in IBD [73]. Considering that chensinin-1b was demonstrated to be effective against a diverse range of microbiota [54,55,67], in the future, it will be necessary to investigate whether the therapeutic effects of chensinin-1b on colitis are correlated with alterations in the gut microbiota beyond direct regulation of macrophage polarization. Due to the intricate nature of IBD and the beneficial role of M2 macrophages in repairing IBD-associated barrier defects, further investigation is warranted to elucidate the potential of chensinin-1b in IBD intervention, epithelial barrier restoration, and gut microbiota modulation.…”

Section: Discussionmentioning

confidence: 99%

Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype

Sun,

Li,

Duan

et al. 2024

Biomedicines

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Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with an increasing prevalence worldwide. Macrophage polarization is involved in the pathogenesis of IBD. Repolarization of macrophage has thus emerged as a novel therapeutic approach for managing IBD. Chensinin-1b, derived from the skin of Rana chensinensis, is a derivative of a native antimicrobial peptide (AMP). It shows anti-inflammatory effects in sepsis models and can potentially modulate macrophage polarization. The objective of this research was to study the role of chensinin-1b in macrophage polarization and dextran sulfate sodium (DSS)-induced colitis. RAW264.7 macrophages were polarized to the M1 phenotype using lipopolysaccharide (LPS) and simultaneously administered chensinin-1b at various concentrations. The ability of chenisnin-1b to reorient macrophage polarization was assessed by ELISA, qRT-PCR, and flow cytometry analysis. The addition of chensinin-1b significantly restrained the expression of M1-associated proinflammatory cytokines and surface markers, including TNF-α, IL-6, NO, and CD86, and exaggerated the expression of M2-associated anti-inflammatory cytokines and surface markers, including IL-10, TGF-β1, Arg-1, Fizz1, Chil3, and CD206. Mechanistically, via Western Blotting, we revealed that chensinin-1b induces macrophage polarization from the M1 to the M2 phenotype by inhibiting the phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In mouse models of colitis, intraperitoneal administration of chensinin-1b alleviated symptoms induced by DSS, including weight loss, elevated disease activity index (DAI) scores, colon shortening, colonic tissue damage, and splenomegaly. Consistent with our in vitro data, chensinin-1b induced significant decreases in the expression of M1 phenotype biomarkers and increases in the expression of M2 phenotype biomarkers in the mouse colitis model. Furthermore, chensinin-1b treatment repressesed NF-κB phosphorylation in vivo. Overall, our data showed that chensinin-1b attenuates IBD by repolarizing macrophages from the M1 to the M2 phenotype, suggesting its potential as a therapeutic candidate for IBD.

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Structure-activity analysis and biological studies of chensinin-1b analogues

Cited by 12 publications

References 33 publications

Characterization and Antimicrobial Activity of Amphiphilic Peptide AP3 and Derivative Sequences

Characterization and Antimicrobial Activity of Amphiphilic Peptide AP3 and Derivative Sequences

Targeted Modification and Structure-Activity Study of GL-29, an Analogue of the Antimicrobial Peptide Palustrin-2ISb

Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype

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