Designed peptide with a flexible central motif from ranatuerins adapts its conformation to bacterial membranes

Juretić, Davor; Sonavane, Yogesh; Ilić, Nada; Gajski, Goran; Goić-Barišić, Ivana; Tonkić, Marija; Kozic, Mara; Maravić, Ana; Pellay, François-Xavier; Zoranić, Larisa

doi:10.1016/j.bbamem.2018.10.005

Cited by 10 publications

(18 citation statements)

References 83 publications

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“…There are many published reports of anuran AMPs with anticancer activity and selectivity against PC-3 prostate cancer cells [85]. The present paper is the first report about good anticancer activity and selectivity of flexampin [22], a designed analog of adepantin-1 [26,53], and most importantly of novel AMPs found in the Trichoplax adhaerens proteome.…”

Section: Discussionmentioning

confidence: 67%

“…These observations can be compared with predicted amphipathic helical length of 50% for that peptide associated with a membrane. When MD simulations were performed for flexampin attached to or inserted into the anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine:1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol membrane, up to 85% of α-helical conformation was observed [ 22 ], well in concord with the 82% prediction by SPLIT. Accordingly, helical conformation for the remaining six peptides when attached to an anionic membrane ( Table 1 ) is a reasonable assumption.…”

Section: Resultsmentioning

confidence: 83%

“…The MIC and MBC concentrations were presented in our earlier publications for kiadins [ 24 ] and flexampin [ 22 ]. In this paper, we show that two trichoplaxin-2 peptides (T2 and T2R1), a designed adepantin-1 analog (A1A), pexiganan analog (PEXA), MAP analog (MAPA), and ZYK1 have equally good activity in a low micromolar range from 0.25 to 2 μM ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…In most cases, it is bracketed with hydrophobic residues, which results in a high predicted alpha hydrophobic moment for a sequence segment containing the KK doublet. For A1A, PEXA, MAPA, T2R1, and ZYK1 (this work), and FLEX [22], one or more doublets of cationic residues combine with hydrophobic residues in such a way to facilitate predicted folding into an amphipathic helical conformation.…”

Section: Effect Of Amphipathic Motifs On Activitymentioning

confidence: 99%

“…This paper aims to present the design and multifunctional screening of nine AMPs, some new and some described in our recent publications [22][23][24], for their in vitro performance as wide-spectrum antimicrobial and anticancer peptides. We define the overall performance as the product of peptide activity and selectivity.…”

Section: Introductionmentioning

confidence: 99%

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The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

et al. 2020

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The link between the antimicrobial and anticancer activity of peptides has long been studied, and the number of peptides identified with both activities has recently increased considerably. In this work, we hypothesized that designed peptides with a wide spectrum of selective antimicrobial activity will also have anticancer activity, and tested this hypothesis with newly designed peptides. The spectrum of peptides, used as partial or full design templates, ranged from cell-penetrating peptides and putative bacteriocin to those from the simplest animals (placozoans) and the Chordata phylum (anurans). We applied custom computational tools to predict amino acid substitutions, conferring the increased product of bacteriostatic activity and selectivity. Experiments confirmed that better overall performance was achieved with respect to that of initial templates. Nine of our synthesized helical peptides had excellent bactericidal activity against both standard and multidrug-resistant bacteria. These peptides were then compared to a known anticancer peptide polybia-MP1, for their ability to kill prostate cancer cells and dermal primary fibroblasts. The therapeutic index was higher for seven of our peptides, and anticancer activity stronger for all of them. In conclusion, the peptides that we designed for selective antimicrobial activity also have promising potential for anticancer applications.

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Section: Discussionmentioning

confidence: 67%

Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Effect Of Amphipathic Motifs On Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

et al. 2020

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A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs

Fong-Coronado,

Ramirez,

Quintero-Hernández

et al. 2024

J Membrane Biol

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Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13–25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs. Graphical Abstract

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Anisaxins, helical antimicrobial peptides from marine parasites, kill resistant bacteria by lipid extraction and membrane disruption

et al. 2022

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Designed peptide with a flexible central motif from ranatuerins adapts its conformation to bacterial membranes

Cited by 10 publications

References 83 publications

The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs

Anisaxins, helical antimicrobial peptides from marine parasites, kill resistant bacteria by lipid extraction and membrane disruption

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