Novel chimeric peptide with enhanced cell specificity and anti-inflammatory activity

Kim, Young‐Min; Kim, Nam-Hong; Lee, Jong-Wan; Jang, Jae-Dong; Park, Yung-Hoon; Park, Seong-Cheol; Jang, Mi-Kyeong

doi:10.1016/j.bbrc.2015.05.063

Cited by 11 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the antifungal activity of Hn-Mc was similar to that of the parent peptides, HPA3NT3 and ME, our results suggest that the Hn-Mc peptide may be the only alternative antibiotic because the cytotoxic activity of Hn-Mc decreased remarkably in comparison to that of the two peptides, as reported previously [ 12 ].…”

Section: Resultssupporting

confidence: 83%

“…The combined peptide contained an equal distribution of hydrophobic and hydrophilic amino acid residues to HPA3NT3. This peptide has strong antibacterial activity against various pathogenic strains of drug-susceptible/resistant bacteria by damaging the cell wall, and with lower cytotoxicity than the parent peptides This indicates that Hn-Mc is an excellent model peptide with potent antibacterial activity and non-cytotoxicity [ 12 ]. However, the antifungal activity and the mechanism of action of a chimeric peptide remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antifungal Effect of A Chimeric Peptide Hn-Mc against Pathogenic Fungal Strains

et al. 2020

Self Cite

View full text Add to dashboard Cite

It is difficult to identify new antifungal agents because of their eukaryotic nature. However, antimicrobial peptides can well differentiate among cell types owing to their variable amino acid content. This study aimed to investigate the antifungal effect of Hn-Mc, a chimeric peptide comprised of the N-terminus of HPA3NT3 and the C-terminus of melittin. We evaluated its potent antifungal activity at low minimal inhibitory concentrations (MICs) ranging from 1–16 μM against pathogenic yeast and molds. The cell-type specificity of Hn-Mc was mediated through the formation of a random α-helical structure to mimic the fungal membrane environment. Furthermore, Hn-Mc caused cell death in C. tropicalis and F. oxysporum by inducing apoptosis via the generation of reactive oxygen species (ROS) due to mitochondrial damage. The present results indicate that Hn-Mc has a high affinity for the fungal plasma membrane and induces apoptosis in fungal cells, and provide guidance for the development of new antifungal agents.

show abstract

Section: Resultssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Antifungal Effect of A Chimeric Peptide Hn-Mc against Pathogenic Fungal Strains

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Melittin has been widely studied using many model systems as well as many biological systems. In cells, melittin was first identified as a “direct lytic factor” in bee venom as it induced hemolysis. , Different groups have also modified melittin and used hemolysis to better understand its binding and permeabilizing effect in erythrocytes. ,,− The hemolysis and leakage assays have also been used to study potential therapeutic applications of melittin. − Unlike the majority of MPPs, which have some selectivity, melittin has remarkably consistent activity against various types of biological membranes. Against eukaryotic cell membranes, including erythrocytes and nucleated cells, melittin causes complete osmotic lysis at concentrations of around 5 μM. − ,,− Similarly, ∼5 μM melittin has sterilizing activity against most Gram negative and Gram positive bacteria, due to membrane permeabilization. ,,, These experiments, especially LDH release and hemolysis, have also been used to study another extensively investigated peptide, magainin 2. ,, The cytolytic effect of many MPPs including defensins, penetratin, and TAT have also been described using the above assays. ,,− …”

Section: Systems For Studying Membrane Permeabilizing Peptidesmentioning

confidence: 99%

Mechanistic Landscape of Membrane-Permeabilizing Peptides

et al. 2019

View full text Add to dashboard Cite

Membrane permeabilizing peptides (MPPs) are as ubiquitous as the lipid bilayer membranes they act upon. Produced by all forms of life, most membrane permeabilizing peptides are used offensively or defensively against the membranes of other organisms. Just as nature has found many uses for them, translational scientists have worked for decades to design or optimize membrane permeabilizing peptides for applications in the laboratory and in the clinic ranging from antibacterial and antiviral therapy and prophylaxis to anticancer therapeutics and drug delivery. Here, we review the field of membrane permeabilizing peptides. We discuss the diversity of their sources and structures, the systems and methods used to measure their activities, and the behaviors that are observed. We discuss the fact that “mechanism” is not a discrete or a static entity for an MPP but rather the result of a heterogeneous and dynamic ensemble of structural states that vary in response to many different experimental conditions. This has led to an almost complete lack of discrete three-dimensional active structures among the thousands of known MPPs and a lack of useful or predictive sequence-structure–function relationship rules. Ultimately, we discuss how it may be more useful to think of membrane permeabilizing peptides mechanisms as broad regions of a mechanistic landscape rather than discrete molecular processes.

show abstract

“…It has been well accepted that antimicrobial peptides target and disintegrate a bacterial cell membrane through electrostatic interactions and induce pore formation, consequently causing cell death . Antimicrobial peptides exert a rapid and highly potent broad spectrum of antimicrobial activities against microorganism with a low tendency to induce bacterial resistance. , We have recently developed a novel chimeric peptide (HnMc) as a new class of antimicrobial peptides . HnMc was developed by combining the N-terminus of HPA3NT3 (an analogue Helicobacter pylori ribosomal protein L1) and the C-terminus of melittin.…”

Section: Introductionmentioning

confidence: 99%

“…13,15 We have recently developed a novel chimeric peptide (HnMc) as a new class of antimicrobial peptides. 16 HnMc was developed by combining the Nterminus of HPA3NT3 (an analogue Helicobacter pylori ribosomal protein L1) and the C-terminus of melittin. Chimeric HnMc was found to target plasma membranes of microbes and damage the membrane envelope, killing a number of drug-susceptible bacteria and drug-resistant bacteria, with excellent cell selectivity and a minimal inhibitory concentration (MIC) of less than 2 μM.…”

Section: Introductionmentioning

confidence: 99%

Imaging and Targeted Antibacterial Therapy Using Chimeric Antimicrobial Peptide Micelles

Park

Ko²,

Hyeon³

et al. 2020

ACS Appl. Mater. Interfaces

Self Cite

View full text Add to dashboard Cite

Infectious diseases induced by multidrug-resistant bacteria are a challenging problem in medicine because of global rise in the drug resistance to pathogenic bacteria. Despite great efforts on the development of antibiotics and antimicrobial agents, there is still a great need to develop a strategy to early detect bacterial infections and eradicate bacteria effectively and simultaneously. The innate immune systems of various organisms produce antimicrobial peptides, which kill a broad range of bacteria with minimal cytotoxicity to mammalian cells. Therefore, antimicrobial peptides have recently attracted increasing attention as an alternative to conventional antibiotics in antibacterial medications. Here, we report a new family of antibacterial agents, which is formulated from self-assembly of a chimeric antimicrobial lipopeptide (DSPE-HnMc) and amphiphilic biodegradable polymers. HnMc micelles could effectively bind the bacterial membrane to kill a wide spectrum of bacteria and bacterial biofilms. In the studies of mouse models of drug-resistant bacterial infections, HnMc micelles could target bacterial infections with high specificity and also kill drug-resistant bacteria effectively, demonstrating the great potential of HnMc micelles as imaging and targeted antibacterial agents. These findings also provide new insight into the design of antimicrobial peptide-based nanomedicine for detection and treatment of bacterial infections.

show abstract

Novel chimeric peptide with enhanced cell specificity and anti-inflammatory activity

Cited by 11 publications

References 43 publications

Antifungal Effect of A Chimeric Peptide Hn-Mc against Pathogenic Fungal Strains

Antifungal Effect of A Chimeric Peptide Hn-Mc against Pathogenic Fungal Strains

Mechanistic Landscape of Membrane-Permeabilizing Peptides

Imaging and Targeted Antibacterial Therapy Using Chimeric Antimicrobial Peptide Micelles

Contact Info

Product

Resources

About