Antibacterial Properties and Mode of Action of a Short Acyl-Lysyl Oligomer

@article{Zaknoon2009AntibacterialPA,
  title={Antibacterial Properties and Mode of Action of a Short Acyl-Lysyl Oligomer},
  author={Fadia Zaknoon and H. Sarig and S. Rotem and L. Livne and A. Ivankin and D. Gidalevitz and A. Mor},
  journal={Antimicrobial Agents and Chemotherapy},
  year={2009},
  volume={53},
  pages={3422 - 3429}
}
ABSTRACT We investigated the potency, selectivity, and mode of action of the oligo-acyl-lysine (OAK) NC12-2β12, which was recently suggested to represent the shortest OAK sequence that retains nonhemolytic antibacterial properties. A growth inhibition assay against a panel of 48 bacterial strains confirmed that NC12-2β12 exerted potent activity against gram-positive bacteria while exhibiting negligible hemolysis up to at least 100 times the MIC. Interestingly, NC12-2β12 demonstrated a… Expand
Design and characterization of a broad -spectrum bactericidal acyl-lysyl oligomer.
TLDR
Investigation of OAK sequences and characterized a promising representative, designated C(12)K-3beta(10), with broad-spectrum activity and low hemotoxicity, which demonstrated the OAK's ability to significantly affect bacterial viability upon single-dose systemic treatment. Expand
Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes.
TLDR
It is found guanidino group-containing chimeras to exhibit greater disruptive activity on DPPG monolayers than the amino group- containing analogues, however, this effect was not observed for lipopolysaccharide monolayer where the difference was negligible. Expand
Synthesis, antibacterial activity and mode of action of novel linoleic acid-dipeptide-spermidine conjugates.
TLDR
The designed template, based on a novel hydrophobic-dipeptide-spermidine template, may prove to be a suitable probe to optimize sequences for better selectivity and potential to combat a wide range of drug resistant strains in further research. Expand
De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities
TLDR
The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics. Expand
Antiplasmodial Properties of Acyl-Lysyl Oligomers in Culture and Animal Models of Malaria
TLDR
The ability of various octanoyl-based OAKs to distinctively affect ring and trophozoite stages of the parasite developmental cycle suggests a distinct antiplasmodial mechanism, nonmembranolytic to host red blood cells (RBCs). Expand
Bacterial membrane activity of α-peptide/β-peptoid chimeras: Influence of amino acid composition and chain length on the activity against different bacterial strains
TLDR
It was found that chain length but not type of cationic amino acid influenced the antibacterial activity of a series of synthetic α-peptide/peptoid chimeras, and the outer membrane may act as a barrier in Gram-negative bacteria. Expand
Synthetic mimics of antimicrobial peptides from triaryl scaffolds.
TLDR
It was found that the overall hydrophobicity had a more significant impact on antimicrobial and hemolytic activity than the conformational stiffness. Expand
Antimicrobial Peptides Targeting Gram-Positive Bacteria
TLDR
The multifaceted mode of actions will make AMPs superior to antibiotics that act only on one specific target, whereupon most of these peptides are supposed to kill bacteria via membrane damage. Expand
OAK-based cochleates as a novel approach to overcome multidrug resistance in bacteria.
TLDR
Single-dose administration of erythromycin coencapsulated in OAK-based cochleates has decreased drug toxicity and increased therapeutic efficacy in a dose-dependent manner, suggesting a potentially useful approach for fighting efflux-enhanced resistance mechanisms. Expand
The antibacterial activity of BF-30 in vitro and in infected burned rats is through interference with cytoplasmic membrane integrity
TLDR
Dose-response studies indicated that BF-30 significantly reduced the colonization of P. aeruginosa in the burn eschars, lungs and liver of burn injured rats and that it could prevent subsequent systemic infection and development of inflammation, demonstrating potential therapeutic value for the prevention and treatment of burn and wound infections. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 62 REFERENCES
Analogous oligo‐acyl‐lysines with distinct antibacterial mechanisms
TLDR
The data support the view that the analogous OAKs induced bacterial death by distinct mechanisms and suggest that relatively minor differences in the sequence of host defense peptides are responsible for selecting one mechanism over another, possibly in conjunction with differential binding affinities to the external and/or cytoplasmic membrane. Expand
Structure-activity relationships of antibacterial acyl-lysine oligomers.
We describe structure-activity relationships that emerged from biophysical data obtained with a library of antimicrobial peptide mimetics composed of 103 oligoacyllysines (OAKs) designed to pin downExpand
Antiplasmodial Activity of Lauryl-Lysine Oligomers
TLDR
An oligoacyllysine (OAK) tetramer designed to mimic the characteristics of dermaseptin was synthesized and assessed for its antimalarial activity, revealing that the ring and trophozoite stages of the parasite developmental cycle were equally sensitive to the compound. Expand
Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides
TLDR
The in vitro activities of ampetoids are strikingly similar to those of AMPs themselves, suggesting a strong mechanistic analogy, and add to the growing evidence that nonnatural foldamers will emerge as an important class of therapeutics. Expand
Systemic Antibacterial Activity of Novel Synthetic Cyclic Peptides
TLDR
The results suggest that these amphipathic cyclic d,l-α-peptides have potential for systemic administration and treatment of otherwise antibiotic-resistant infections. Expand
Impact of Self-Assembly Properties on Antibacterial Activity of Short Acyl-Lysine Oligomers
TLDR
The data indicated that the higher efficiency in interfering with bacterial viability emanated from a wobbly packing imposed by a single double bond, which suggests that similar strategies might improve hydrophobic OAKs and related lipopeptide antibiotics. Expand
In vitro discriminative antipseudomonal properties resulting from acyl substitution of N-terminal sequence of dermaseptin s4 derivatives.
TLDR
Various mechanistic studies failed to detect significant differences in secondary structure, bactericidal kinetics, or ability to perturb the cytoplasmic membrane, pointing to a similar mode of action. Expand
Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli.
TLDR
It was demonstrated that individual peptides varied widely in their ability to depolarize the cytoplasmic membrane potential of E. coli, with certain peptides such as the loop peptide bactenecin and the alpha-helical peptide CP26 being unable to cause depolarization at the minimal inhibitory concentration (MIC), and others like gramicidin S causing maximal depolarized below the MIC. Expand
Bacterial membranes as predictors of antimicrobial potency.
TLDR
It is demonstrated, using members of a novel class of antimicrobial agents, the oligomers of acyllysine, that one cause for the difference in species selectivity is the ability to induce the clustering of anionic lipids, resulting in their segregation into domains. Expand
Sublethal Concentrations of Pleurocidin-Derived Antimicrobial Peptides Inhibit Macromolecular Synthesis in Escherichia coli
TLDR
Results indicate that peptides at their lowest inhibitory concentrations may be less capable of damaging cell membranes, while they maintain their ability to inhibit macromolecular synthesis. Expand
...
1
2
3
4
5
...