In Vitro ADME Properties of Two Novel Antimicrobial Peptoid-Based Compounds as Potential Agents against Canine Pyoderma

Greco, Ines; Hummel, Bernard D; Vasir, Jaspreet K.; Watts, Jeffrey L.; Koch, Jason; Hansen, Johannes E.; Nielsen, Hanne Mørck; Damborg, Peter; Pb, Hansen

doi:10.3390/molecules23030630

Cited by 13 publications

(10 citation statements)

References 61 publications

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“…However, the vast literature and clinical trials on AMPs did not result in systemic therapy and treatments [ 151 ]. AMPs are active selectively at micromolar concentrations and prone to have their chemical synthesis optimized despite their short half-life in vivo and high scaling-up costs of production making difficult the commercial uses [ 25 , 152 ]. De novo design of AMPs following a peptide-mimetic approach [ 153 ] yields peptoids [ 154 , 155 , 156 ], peptide–peptoid hybrids [ 157 ] and α-peptide/β-peptoids [ 158 ] with increased in vivo stability and resistance against proteolytic degradation.…”

Section: Bsa With Peptidesmentioning

confidence: 99%

“…De novo design of AMPs following a peptide-mimetic approach [ 153 ] yields peptoids [ 154 , 155 , 156 ], peptide–peptoid hybrids [ 157 ] and α-peptide/β-peptoids [ 158 ] with increased in vivo stability and resistance against proteolytic degradation. Most studies have been performed with short peptoids up to four residues.For example, a recent study described a peptide-peptoid hybrid, B1, and a peptoid, D2, that were highly active against Staphylococcus pseudintermedius (MIC 2–4 µg/mL) and exhibited potential as topical treatment against canine pyoderma [ 152 ]. Figure 9 illustrates the chemical structure of these interesting peptidomimetic molecules obtained by copying AMPs regarding their hydrophobicity and cationic character which gather positively charged and hydrophobic moieties for optimal activity as reproduced from [ 152 ].…”

Section: Bsa With Peptidesmentioning

confidence: 99%

“… Chemical structures of synthetic peptidomimetic molecules such as a peptide–peptoid hybrid ( A ) and a peptoid ( B ); both highly active (MIC 2–4 µg/mL) for treating topical infections in dogs caused by Staphylococcus pseudintermedius. Reproduced from [ 152 ]. …”

Section: Figurementioning

confidence: 99%

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Self-Assembled Antimicrobial Nanomaterials

Carmona-Ribeiro

2018

IJERPH

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Nanotechnology came to stay improving the quality of human life by reducing environmental contamination of earth and water with pathogens. This review discusses how self-assembled antimicrobial nanomaterials can contribute to maintain humans, their water and their environment inside safe boundaries to human life even though some of these nanomaterials display an overt toxicity. At the core of their strategic use, the self-assembled antimicrobial nanomaterials exhibit optimal and biomimetic organization leading to activity at low doses of their toxic components. Antimicrobial bilayer fragments, bilayer-covered or multilayered nanoparticles, functionalized inorganic or organic polymeric materials, coatings and hydrogels disclose their potential for environmental and public health applications in this review.

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Section: Bsa With Peptidesmentioning

confidence: 99%

Section: Bsa With Peptidesmentioning

confidence: 99%

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Self-Assembled Antimicrobial Nanomaterials

Carmona-Ribeiro

2018

IJERPH

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“…Thus, they act quickly and selectively against bacteria at micromolar concentrations [9]. AMPs, as the next generation of antibacterials, are the object of rapidly-growing research interest and may also be promising antimicrobials for the treatment of staphylococcal skin infections in dogs, particularly where antibiotic therapy may be limited because of multidrug resistance [10].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Efficiency of Antimicrobial Peptides against Staphylococcal Pathogens Associated with Canine Pyoderma

Jarosiewicz

Garbacz

Neubauer

et al. 2020

Animals

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The emergence of staphylococcal canine pathogens resistant to multiple antimicrobial agents is a growing and urgent problem in veterinary practice. Antimicrobial peptides (AMPs) seem to be a promising alternative to conventional antibiotics. The aim of this in vitro study was to evaluate the antimicrobial activity of selected AMPs against pathogenic staphylococcal strains, including multidrug- and methicillin-resistant strains isolated from canine pyoderma cases. Seven antimicrobial peptides (aurein 1.2, CAMEL, citropin 1.1, protegrin-1, pexiganan, temporin A and uperin 3.6) synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase method were tested. The minimal inhibitory and minimal bactericidal concentrations (MIC and MBC) were determined by the broth microdilution method. The study showed that analyzed AMPs exerted an extensive effect against canine pathogens, with the most active peptide being uperin 3.6. The tested AMPs were equally efficient against both resistant- and susceptible staphylococcal strains and were more efficient against Staphylococcus pseudintermedius than against Staphylococcus aureus strains. Our findings are particularly interesting from a clinical perspective, as they point to AMPs as potential therapeutic topical agents in canine pyoderma cases associated with antimicrobial resistance of staphylococci.

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“…D2D is a full d-amino acid analog derived from a structure-activity relationship study of the peptoid D2. Furthermore D2, was selected in a previous study after screening from a combinatorial library of de novo designed compounds for their activity against S. pseudintermedius and toxicity in vitro against red blood cells [19].…”

Section: Introductionmentioning

confidence: 99%

Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D

et al. 2019

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The increasing emergence of multi-drug resistant bacteria is a serious threat to public health worldwide. Antimicrobial peptides have attracted attention as potential antibiotics since they are present in all multicellular organisms and act as a first line of defence against invading pathogens. We have previously identified a small all-d antimicrobial octapeptide amide kk(1-nal)fk(1-nal)k(nle)-NH 2 (D2D) with promising antimicrobial activity. In this work, we have performed a structure-activity relationship study of D2D based on 36 analogues aimed at discovering which elements are important for antimicrobial activity and toxicity. These modifications include an alanine scan, probing variation of hydrophobicity at lys 5 and lys 7 , manipulation of amphipathicity, N-and C-termini deletions and lys-arg substitutions. We found that the hydrophobic residues in position 3 (1-nal), 4 (phe), 6 (1-nal) and 8 (nle) are important for antimicrobial activity and to a lesser extent cationic lysine residues in position 1, 2, 5 and 7. Our best analogue 5, showed MICs of 4 µg/mL against A. baumannii, E. coli, P. aeruginosa and S. aureus with a hemolytic activity of 47% against red blood cells. Furthermore, compound 5 kills bacteria in a concentration-dependent manner as shown by time-kill kinetics. Circular dichroism (CD) spectra of D2D and compounds 1-8 showed that they likely fold into α-helical secondary structure. Small angle x-ray scattering (SAXS) experiments showed that a random unstructured polymer-like chains model could explain D2D and compounds 1, 3, 4, 6 and 8. Solution structure of compound 5 can be described with a nanotube structure model, compound 7 can be described with a filament-like structure model, while compound 2 can be described with both models. Lipid interaction probed by small angle X-ray scattering (SAXS) showed that a higher amount of compound 5 (~50-60%) inserts into the bilayer compared to D2D (~30-50%). D2D still remains the lead compound, however compound 5 is an interesting antimicrobial peptide for further investigations due to its nanotube structure and minor improvement to antimicrobial activity compared to D2D.

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In Vitro ADME Properties of Two Novel Antimicrobial Peptoid-Based Compounds as Potential Agents against Canine Pyoderma

Cited by 13 publications

References 61 publications

Self-Assembled Antimicrobial Nanomaterials

Self-Assembled Antimicrobial Nanomaterials

In Vitro Efficiency of Antimicrobial Peptides against Staphylococcal Pathogens Associated with Canine Pyoderma

Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D

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