Publications by authors named "Marta De Zotti"

Article Synopsis
  • Pseudomonas syringae causes significant plant diseases, and traditional treatments like copper and antibiotics raise environmental concerns; antimicrobial peptides (AMPs) from fungi could offer a safer option.
  • The study focuses on trichogin GA IV, a fungal AMP, examining modifications that increase its effectiveness against P. syringae, which affects crops like tomatoes and kiwifruits.
  • Results reveal that modified analogs with glycine-to-lysine changes show strong antibacterial properties, especially tri-lysine versions, which significantly reduce bacterial presence and symptoms in infected tomato plants.
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We recently reported a new technique, light-induced triplet-triplet electron resonance (LITTER) spectroscopy, which allows quantification of the dipolar interaction between the photogenerated triplet states of two chromophores. Here we carry out a systematic LITTER study, considering orientation selection by the detection pulses, of a series of bis-porphyrin model peptides with different porphyrin-porphyrin distances and relative orientations. Orientation-dependent analysis of the dipolar datasets yields conformational information of the molecules in frozen solution which is in good agreement with density functional theory predictions.

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To carry out reliable and comprehensive structural investigations, the exploitation of different complementary techniques is required. Here, we report that dual triplet-spin/fluorescent labels enable the first parallel distance measurements by electron spin resonance (ESR) and Förster resonance energy transfer (FRET) on exactly the same molecules with orthogonal chromophores, allowing for direct comparison. An improved light-induced triplet-triplet electron resonance method with 2-color excitation is used, improving the signal-to-noise ratio of the data and yielding a distance distribution that provides greater insight than the single distance resulting from FRET.

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Peptaibols are proteolysis-resistant, membrane-active peptides. Their remarkably stable helical 3D-structures are key for their bioactivity. They can insert themselves into the lipid bilayer as barrel staves, or lay on its surface like carpets, depending on both their length and the thickness of the lipid bilayer.

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Antimicrobial peptides (AMPs) represent a promising class of compounds to fight resistant infections. They are commonly thought to kill bacteria by perturbing the permeability of their cell membranes. However, bacterial killing requires a high coverage of the cell surface by bound peptides, at least in the case of cationic and amphipathic AMPs.

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Heat shock protein 90 (Hsp90) and cell division cycle 37 (Cdc37) work together as a molecular chaperone complex to regulate the activity of a multitude of client protein kinases. These kinases belong to a wide array of intracellular signaling networks that mediate multiple cellular processes including proliferation. As a result, Hsp90 and Cdc37 represent innovative therapeutic targets in various cancers (such as leukemia, multiple myeloma, and hepatocellular carcinoma (HCC)) in which their expression levels are elevated.

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New classes of antibacterial drugs are urgently needed to address the global issue of antibiotic resistance. In this context, peptaibols are promising membrane-active peptides since they are not involved in innate immunity and their antimicrobial activity does not involve specific cellular targets, therefore reducing the chance of bacterial resistance development. Trichogin GA IV is a nonhemolytic, natural, short-length peptaibol active against Gram-positive bacteria and resistant to proteolysis.

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In the large field of bioactive peptides, peptaibols represent a unique class of compounds. They are membrane-active peptides, produced by fungi of the genus and known to elicit plant defenses. Among the short-length peptaibols, trichogin GA IV is nonhemolytic, proteolysis-resistant, antibacterial, and cytotoxic.

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Black rot caused by the Gram-negative bacterial pathogen pv. (Xcc) is considered one of the most destructive diseases affecting crucifers. Xcc is a seedborne pathogen able to infect the host at any growth stage.

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Article Synopsis
  • The grapevine downy mildew is a serious problem for grape growers, causing a lot of damage and is usually treated with chemical sprays called fungicides.
  • Scientists are looking for safer alternatives to these chemicals and found a special peptide called 4r that can help stop the disease.
  • In tests, this peptide worked really well in the fields, reducing the disease without harming the plants, and it might also work against other types of fungi.
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Peptaibols are naturally occurring, antimicrobial peptides endowed with well-defined helical conformations and resistance to proteolysis. Both features stem from the presence in their sequence of several, C -tetrasubstituted, α-aminoisobutyric acid (Aib) residues. Peptaibols interact with biological membranes, usually causing their leakage.

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Article Synopsis
  • Researchers introduced a new photoswitchable spin label, erythrosin B, for enhanced electron paramagnetic resonance spectroscopy, specifically for biological studies.
  • The study explores how orientational effects impact distance measurements between spin labels in a peptide, achieving results that align well with theoretical predictions.
  • The method is practical at higher temperatures, reducing costs associated with traditional cooling techniques, making LiPDS more accessible for structural biology research.
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Peptaibols are non-ribosomal linear peptides naturally produced by a wide variety of fungi and represent the largest group of peptaibiotic molecules produced by species. Trichogin GA IV is an 11-residue peptaibol naturally produced by . Peptaibols possess the ability to form pores in lipid membranes or perturb their surface, and have been studied as antibiotics or anticancer drugs in human medicine, or as antimicrobial molecules against plant pathogens.

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Membrane-active peptides are a promising class of antimicrobial and anticancer therapeutics. For this reason, their molecular mechanisms of action are currently actively investigated. By exploiting Electron Paramagnetic Resonance, we study the membrane interaction of two spin-labeled analogs of the antimicrobial and cytotoxic peptide trichogin GA IV (Tri), with opposite bioactivity: Tri(Api), able to selectively kill cancer cells, and Tri(Leu), which is completely nontoxic.

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Eco-friendly analogs of Trichogin GA IV, a short peptaibol produced by , were assayed against , the causal agent of rice blast disease. and screenings allowed us to identify six peptides able to reduce by about 70% rice blast symptoms. One of the most active peptides was selected for further studies.

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Peptaibols, by disturbing the permeability of phospholipid membranes, can overcome anticancer drug resistance, but their natural hydrophobicity hampers their administration. By a green peptide synthesis protocol, we produced two water-soluble analogs of the peptaibol trichogin GA IV, termed K6-Lol and K6-NH2. To reduce production costs, we successfully explored the possibility of changing the naturally occurring 1,2-aminoalcohol leucinol to a C-terminal amide.

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Article Synopsis
  • Tylopeptin B is a peptide with antibacterial properties against Gram-positive bacteria, working by altering bacterial membrane characteristics and increasing permeability, often through self-assembling into channels.
  • Research using pulsed double electron-electron resonance (DEER) shows that Tylopeptin B begins to self-assemble at low concentrations (0.1 mol%) and forms stable clusters at higher concentrations (above 0.2 mol%) with an average cluster size of about 3.3 peptides.
  • DEER and electron spin echo envelope modulation (ESEEM) techniques indicate that at concentrations from 0.1 to 0.2 mol%, Tylopeptin B clusters repel
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We present a new technique, light-induced triplet-triplet electron resonance spectroscopy (LITTER), which measures the dipolar interaction between two photoexcited triplet states, enabling both the distance and angular distributions between the two triplet moieties to be determined on a nanometer scale. This is demonstrated for a model bis-porphyrin peptide that renders dipolar traces with strong orientation selection effects. Using simulations and density functional theory calculations, we extract distance distributions and relative orientations of the porphyrin moieties, allowing the dominant conformation of the peptide in a frozen solution to be identified.

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External stimuli are potent tools that Nature uses to control protein function and activity. For instance, during viral entry and exit, pH variations are known to trigger large protein conformational changes. In Nature, also the electron transfer (ET) properties of ET proteins are influenced by pH-induced conformational changes.

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Fungal species belonging to the genus are commonly used as biocontrol agents against several crop pathogens. Among their secondary metabolites, peptaibols are helical, antimicrobial peptides, which are structurally stable even under extreme pH and temperature conditions. The promise of peptaibols as agrochemicals is, however, hampered by poor water solubility, which inhibits efficient delivery for practical use in crop protection.

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The influence of conformational dynamics on the self-assembly process of a conformationally constrained analogue of the natural antimicrobial peptide Trichogin GA IV was analysed by spectroscopic methods, microscopy imaging at nanometre resolution, and molecular dynamics simulations. The formation of peptide films at the air/water interface and their deposition on a graphite or a mica substrate were investigated. A combination of experimental evidence with molecular dynamics simulation was used to demonstrate that only the fully developed helical structure of the analogue promotes formation of ordered aggregates that nucleate the growth of micrometric rods, which give rise to homogenous coating over wide regions of the hydrophilic mica.

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In frozen biological media and molecular glasses only restricted motions exist; because of the weakness and disorder of intermolecular bonds these motions may have stochastic nature. Electron spin echo (ESE) spectroscopy of spin-labeled molecules allows detecting their restricted stochastic rotations (stochastic molecular librations). As in molecular disordered media motions may be highly cooperative, it would be desirable to investigate their spectroscopic manifestation also in the systems where cooperative effects would be certainly ruled out.

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Trichogin GA IV is a short peptaibol with antimicrobial activity. This uncharged, but amphipathic, sequence is aligned at the membrane interface and undergoes a transition to an aggregated state that inserts more deeply into the membrane, an assembly that predominates at a peptide-to-lipid ratio (P/L) of 1:20. In this work, the natural trichogin sequence was prepared and reconstituted into oriented lipid bilayers.

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Trichogin is a natural peptide endowed with antimicrobial and antitumor activity. A member of the peptaibol family, trichogin possesses a C-terminal amino alcohol. In the past, this moiety was substituted for a methyl ester for synthetic purposes and it was observed that this apparently slight modification caused significant changes in the peptide bioactivity.

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