Search Results (175)

Experimental and theoretical studies were applied to investigate the adsorption properties of testagen (KEDG) peptide on copper surfaces in sodium chloride solution and, implicitly, its inhibition efficiency (IE) on metal corrosion. The tetrapeptide synthesized from the amino acids lysine (Lys), glutamic acid (Glu), aspartic acid (Asp), and glycine (Gly), named as H-Lys-Glu-Asp-Gly-OH, achieved an inhibition efficiency of around 86% calculated from electrochemical measurements, making KEDG a promising new copper corrosion inhibitor. The experimental data were best fitted to the Freundlich adsorption isotherm. The standard free energy of adsorption ($\mathsf{\Delta }{\mathrm{G}}_{\mathrm{a}\mathrm{d}\mathrm{s}}^{\mathrm{o}}$) reached the value of −30.86 kJ mol⁻¹, which revealed a mixed action mechanism of tetrapeptide, namely, chemical and physical spontaneous adsorption. The copper surface characterization was performed using optical microscopy and SEM/EDS analysis. In the KEDG presence, post-corrosion, SEM images showed a network surface morphology including microdeposits with an acicular appearance, and EDS analysis highlighted an upper surface layer consisting of KEDG, sodium chloride, and copper corrosion compounds. The computational study based on DFT and Monte Carlo simulation confirmed the experimental results and concluded that the spontaneous adsorption equilibrium establishment was the consequence of the contribution of noncovalent (electrostatic, van der Waals) interactions and covalent bonds. Full article

In this study, three new 3,7-dihydroxyflavone (1) derivatives with different sugars were designed and synthesised by click chemistry. Click chemistry requires the previously modification of building blocks with azide and alkyne groups and therefore, the 3,7-dihydroxyflavone (1) was first converted in 3,7-(prop-2-yn-yloxy)flavone (2) and acetobromo-α-D-glucose (3) was converted into 2,3,4,6-tetra-O-acetyl-β-glucopyranosyl azide (4). Subsequently, a click reaction was performed via copper-catalysed cycloaddition (CuAAC) between 2 and 4, as well as between 2 and 2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranosyl (AG931) and, 2 and commercial 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl (AG358), resulting in three distinct disubstituted flavone glycosides (5a–5c). Biological assays performed on L929 fibroblast cell lines and human glioblastoma astrocytoma U-251 cell lines indicated cytocompatibility with fibroblasts and reduced metabolic activity of GBM cells in the presence of compound 5b and 5c. To enhance therapeutic effect, improve local drug delivery, and overcome solubility issues of these high molecular weight compounds, the synthesised compounds were encapsulated in polymeric particles (polymersomes, PMs) composed of polylactic acid-polyethylene glycol (PEG-PLA) functionalized, once more by click chemistry, with 0.1 mol% transferrin mimetic (T7—HRPYIAH) peptide. The PMs were prepared by solvent displacement and exhibited stability over 100 days, encapsulation efficiency of 39–93%, and mean size diameters of 120–180 nm. The toxicity assays of the PMs on the U-251 cell line showed a significant decrease in metabolic activity, supporting the potential of this delivery system against GBM. Among the PMs tested, the flavone 5c-based PM demonstrated the highest efficacy. Full article

The mitochondrial phosphate carrier (mPiC), encoded by the nuclear gene SLC25A3, is synthesized with an N-terminus mitochondrial targeting sequence (MTS), enabling its import into the mitochondria. mPiC imports inorganic phosphate (P_i) into the mitochondrial matrix for ATP production and other matrix phosphorylation reactions, as well as regulates mitochondrial Ca²⁺ uptake and buffering of matrix Ca²⁺. PiC also imports copper (Cu), crucial to COX subunit holoenzyme assembly. Variants in SLC25A3 exist and lead to mPiC deficiency (MPCD), cause a rare autosomal recessive disease with no current cure; patients with MPCD usually die within the first year of life. We have developed a novel therapeutic approach using TAT-mPiC fusion protein for cellular delivery since the TAT peptide enables delivery of proteins across biological membranes. We designed, produced, and purified the TAT-mPiC fusion protein. The fusion protein is delivered into the mitochondria and localizes within the mIM, its natural cellular location, as a processed protein. Treatment of mPiC-knockdown cells with TAT-mPiC fusion protein increased cell growth and improved bioenergetic capabilities, as measured by oxygen consumption rate (OCR), ATP production, and reduction in lactate secretion. Most importantly, TAT-mPiC restored P_i and Cu delivery into the mitochondrial matrix. TAT-mPiC fusion protein also restored the mitochondrial activity of cells harboring various mitochondrial defects. This study presents the first successful delivery of a mitochondrial transmembrane carrier using the TAT-fusion system, offering a potential early treatment strategy for newborns with mPiC deficiency. Full article

Burn wounds represent a complex clinical challenge, primarily due to their high susceptibility to infections and the frequent formation of the biofilm, which significantly hinder the healing process. Therefore, effective infection prevention and management are critical components of burn wound care. This review provides a comprehensive overview of the current and emerging antimicrobial strategies in burn management, with a particular focus on alternative approaches to conventional antiseptics and antibiotics. This manuscript highlights the role of metals and metal-based agents, including silver, zinc oxide, and copper compounds, alongside plant-derived bioactive substances such as aloe vera, marigold, and turmeric. Additionally, the potential of antimicrobial peptides and probiotics as innovative therapeutic options is explored, emphasizing their antimicrobial, anti-inflammatory, and pro-healing properties. Finally, this review presents an analysis of recent patents in the field of burn wound care, offering insights into current trends and future directions in the development of advanced wound dressings. By addressing both established and novel strategies, this review aims to provide a valuable resource for clinicians, researchers, and innovators seeking to improve outcomes in burn wound management. Full article

Alum mining leads to significant heavy metal and acid pollution within soils. Phytoremediation is a common strategy used to treat alum mine soils, but its efficiency is frequently compromised by the alum-mining-induced impairment of plant growth. To improve the strength of plants against mine pollution, this study constructed the artificial yeast strain ScHB (heavy metal-binding protein-containing Saccharomyces cerevisiae) expressing the de novo designed protein HBGFP (heavy metal-binding green fluorescence protein) and investigated its effect on the phytoremediation of alum mine soils with soil physiochemical assays and heavy metal quantification. This protein was composed of an N-terminal signal peptide, an HB (heavy metal-binding) domain, and a GFP (green fluorescence protein) domain, as well as a C-terminal glycolphosphatidylinositol-anchoring fragment. The exposure of the HBGFP on the ScHB surface increased the growth rate of the yeast cells and enhanced cadmium capture from the cadmium-containing medium. After culturing Medicago sativa in the alum mine soils for 30 days, ScHB remarkably increased the plants’ average height from 17.5 cm to 27.9 cm and their biomass from 3.03 g/plant to 4.35 g/plant, as well as increasing the accumulation of antioxidant agents in the plants. Moreover, the ScHB cells strongly improved the soil quality, with an increase in the soil pH values from 5.47 to 6.21 to 6.9, and increased the levels of soil organic matter, total nitrogen, available phosphorus, and living bacteria. Furthermore, ScHB efficiently improved the plants’ abilities to remove soil heavy metals, decreasing the levels of cadmium, lead, chromium, and copper by 90%, 86%, 97%, and 88%, respectively. This study developed a genetic engineering method to improve the efficiency of phytoremediation against pollution from alum mining. Full article

Background/Objectives: Antimicrobial resistance (AMR) poses a significant public health threat, leading to increased mortality. The World Health Organization has established a priority list highlighting critical multidrug-resistant (MDR) pathogens that demand urgent research on antimicrobial treatments. Considering this and the fact that new antibiotics are only sporadically approved, natural antibacterial agents have seen a resurgence in interest as potential alternatives to conventional antibiotics and chemotherapeutics. Natural antibacterials, derived from microorganisms, higher fungi, plants, animals, natural minerals, and food sources, offer diverse mechanisms of action against MDR pathogens. Here, we present a comprehensive summary of antibacterial agents from natural sources, including a brief history of their application and highlighting key strategies for using microorganisms (microbiopredators, such as bacteriophages), plant extracts and essential oils, minerals (e.g., silver and copper), as well as compounds of animal origin, such as milk or even venoms. The review also addresses the role of prebiotics, probiotics, and antimicrobial peptides, as well as novel formulations such as nanoparticles. The mechanisms of action of these compounds, such as terpenoids, alkaloids, and phenolic compounds, are explored alongside the challenges for their application, e.g., extraction, formulation, and pharmacokinetics. Conclusions: Future research should focus on developing eco-friendly, sustainable antimicrobial agents and validating their safety and efficacy through clinical trials. Clear regulatory frameworks are essential for integrating these agents into clinical practice. Despite challenges, natural sources offer transformative potential for combating AMR and promoting sustainable health solutions. Full article

Spontaneous cleavage reactions normally occur in vivo on amino acid peptide backbones, leading to fragmentation products that can have different physiological roles and toxicity, particularly when the substrate of the hydrolytic processes are neuronal peptides and proteins highly related to neurodegeneration. We report a hydrolytic study performed with the HPLC-MS technique at different temperatures (4 °C and 37 °C) on peptide fragments of different neuronal proteins (amyloid-β, tau, and α-synuclein) in physiological conditions in the presence of Cu²⁺ and Zn²⁺ ions, two metal ions found at millimolar concentrations in amyloid plaques. The coordination of these metal ions with these peptides significantly protects their backbones toward hydrolytic degradation, preserving the entire sequences over two weeks in solution, while the free peptides in the same buffer are fully fragmented after the same or even shorter incubation period. Our data show that peptide cleavage is not only ruled by the chemical sensitivity of amino acids, but the peptide conformation changes induced by metal coordination influence hydrolytic reactions. The enhanced stability of neuronal peptides provided by metal coordination can increase local levels of amyloidogenic species capable of seeding fibril growth, resulting in aberrant protein depositions and deficits in neuronal activity. Full article

Peptides occupy a significant share of the pharmaceutical market and are among the top-200 selling drugs in the group of non-insulin drugs with analgesic, antibacterial and cardiovascular effects. The aim of this work is to develop a comprehensive analytical approach for quality control of novel synthetic peptides with non-narcotic types of analgesia and to provide docking simulations of dermorphin complex formation at the μ-opioid receptor (MOR) binding site. The materials and methods used include the pharmaceutical substance dermorphin tetrapeptide (DMTP) (tyrosyl-D-arginyl-phenylalanyl-glycinamide); Fourier transform infrared spectroscopy (FT-IR); static and dynamic laser light scattering (DLS, LALLS); scanning optical microscopy (SEM); X-ray fluorescence elements analysis; polarimetry for optical activity determining; and Spirotox method for sample biotesting. FT-IR-Spectra indicated specific amino acid chemical groups in the tetrapeptide sequence at 3300–2700 cm⁻¹, 1670 cm⁻¹. UV-absorption spectra of aqueous solutions of dermorphin tetrapeptide showed an absorption maximum at 275 nm, which is in good agreement with the presented spectrum of the bovine serum albumin (BSA) standard; the Pearson’s r of calibration line “A-C%” in 0.0125% to 0.0500% concentration range is 0.999; and the calculated specific extinction value $E_{1cm }^{1\%}$ = 18.38 ± 0.23. Of the 11 elements detected by X-rays, the elements copper (Cu) and cobalt (Co) have the highest X-ray intensity. Dispersion characteristics of dermorphin solutions were studied in the submicron and micron range. Conglomerates and druzes were detected by SEM, ranging in size from 2 µm to 100 µm. The specific optical activity index was calculated ${\left[\alpha \right]}_D^{20}$ = +36.18 ± 2.04 [°·mL·g⁻¹·dm⁻¹], according to Biot’s Law. Additionally, the orientation and conformation of the dermorphin molecule in the active binding site of the 8E0G receptor were predicted using molecular modeling, revealing that the contact area affects the key amino acid residue arginine (ARG 182). This comprehensive approach to analytical methods for qualitative and quantitative analysis of dermorphin tetrapeptide can be applied in pharmacies to enhance the understanding of its biological activity and aid in the development of regulatory documentation for a new, non-narcotic analgesic based on the dermorphin tetrapeptide. Full article

Based on the established neuroprotective properties of indole-based compounds and their significant potential as multi-targeted therapeutic agents, a series of synthetic indole–phenolic compounds was evaluated as multifunctional neuroprotectors. Each compound demonstrated metal-chelating properties, particularly in sequestering copper ions, with quantitative analysis revealing approximately 40% chelating activity across all the compounds. In cellular models, these hybrid compounds exhibited strong antioxidant and cytoprotective effects, countering reactive oxygen species (ROS) generated by the Aβ(25–35) peptide and its oxidative byproduct, hydrogen peroxide, as demonstrated by quantitative analysis showing on average a 25% increase in cell viability and a reduction in ROS levels to basal states. Further analysis using thioflavin T fluorescence assays, circular dichroism, and computational studies indicated that the synthesized derivatives effectively promoted the self-disaggregation of the Aβ(25–35) fragment. Taken together, these findings suggest a unique profile of neuroprotective actions for indole–phenolic derivatives, combining chelating, antioxidant, and anti-aggregation properties, which position them as promising compounds for the development of multifunctional agents in Alzheimer’s disease therapy. The methods used provide reliable in vitro data, although further in vivo validation and assessment of blood–brain barrier penetration are needed to confirm therapeutic efficacy and safety. Full article

Tyrosinase is a key enzyme responsible for the formation of melanin (a natural skin pigment with ultraviolet-protection properties). However, some people experience melanin overproduction, so new, safe, and biocompatible enzyme inhibitors are sought. New tripeptide tyrosinase inhibitors were developed using molecular modeling. A combinatorial library of tripeptides was prepared and docked to the mushroom tyrosinase crystal structure and investigated with molecular dynamics. Based on the results of calculations and expert knowledge, the three potentially most active peptides (CSF, CSN, CVL) were selected. Their in vitro properties were examined, and they achieved half-maximal inhibitory concentration (IC₅₀) values of 136.04, 177.74, and 261.79 µM, respectively. These compounds attach to the binding pocket of tyrosinase mainly through hydrogen bonds and salt bridges. Molecular dynamics simulations demonstrated the stability of the peptid–tyrosinase complexes and highlighted the persistence of key interactions throughout the simulation period. The ability of these peptides to complex copper ions was also confirmed. The CSF peptide showed the highest chelating activity with copper. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed that none of the test tripeptides showed cytotoxicity toward the reconstructed human epidermis. Our results indicated that the developed tripeptides were non-toxic and effective tyrosinase inhibitors. They could be applied as raw materials in skin-brightening or anti-aging cosmetic products. Full article

This study focuses on the use of three isostructural N₆O donor ligands, specifically known to form complexes with copper ions, to chelate Cu(II) from aqueous solutions. The corresponding Cu(II) complexes feature a dinuclear copper core mimicking the active site of natural superoxide dismutase (SOD) enzymes while also creating a coordination environment favorable for catalase (CAT) activity, being thus appealing as catalytic antioxidant systems. Given the critical role of copper dysregulation in the pathophysiology of Alzheimer’s disease (AD), these complexes may help mitigate the harmful effects of free Cu(II) ions: the goal is to transform copper’s reactive oxygen species (ROS)-generating properties into beneficial ROS-scavenging action. This study investigates the speciation, chelating efficiency, and metal selectivity of these ligands, as well as the antioxidant activity of the resulting complexes under aqueous and physiologically relevant conditions. Additionally, the ligands, equipped with functional groups for attaching targeting moieties, are conjugated with a small peptide that may act as an anti-aggregating agent of β-amyloid peptides, aiming to develop a multifunctional therapeutic strategy against Alzheimer’s disease. Full article

Otitis media (OM) is a frequent disease with incidence rate of 5300 cases per 100,000 people. Recent studies showed that polymicrobial biofilm formation represents a significant pathogenic mechanism in recurrent and chronic forms of OM. Biofilm enables bacteria to resist antibiotics that would typically be recommended in guidelines, contributing to the ineffectiveness of current antimicrobial strategies. Given the challenges of successfully treating bacterial biofilms, there is an growing interest in identifying novel and effective compounds to overcome antibacterial resistance. The objective of this review was to provide an overview of the novel compounds with antibiofilm effects on bacterial biofilm formed by clinical isolates of OM. The systematic review included studies that evaluated antibiofilm effect of novel natural or synthetic compounds on bacterial biofilm formed from clinical isolates obtained from patients with OM. The eligibility criteria were defined using the PICOS system: (P) Population: all human patients with bacterial OM; (I) Intervention: novel natural or synthetic compound with biofilm effect; (C) Control standard therapeutic antimicrobial agents or untreated biofilms, (O) Outcome: antibiofilm effect (biofilm inhibition, biofilm eradication), (S) Study design. The PRISMA protocol for systematic reviews and meta-analysis was followed. From 3564 potentially eligible studies, 1817 duplicates were removed, and 1705 were excluded according to defined exclusion criteria. A total of 41 studies with available full texts were retrieved by two independent authors. Fifteen articles were selected for inclusion in the systematic review which included 125 patients with OM. A total of 17 different novel compounds were examined, including N-acetyl-L-cysteine (NAC), tea tree oil, xylitol, eugenol, Aloe barbadensis, Zingiber officinale, Curcuma longa, Acacia arabica, antisense peptide nucleic acids, probiotics Streptococcus salivarius and Streptococcus oralis, Sodium 2-mercaptoethanesulfonate (MESNA), bioactive glass, green synthesized copper oxide nanoparticles, radish, silver nanoparticles and acetic acid. Staphylococcus aureus was the most commonly studied pathogen, followed by Pseudomonas aeruginosa and Haemophilus influenzae. Biofilm inhibition only by an examined compound was assessed in six studies; biofilm eradication in four studies, and both biofilm inhibition and biofilm eradication were examined in five studies. This systematic review indicates that some compounds like NAC, prebiotics, nanoparticles and MESNA that have significant effects on biofilm are safe and could be researched more extensively for further clinical use. However, a lack of data about reliable and efficient compounds used in therapy of different types of otitis media still remains in the literature. Full article

Copper, along with gold, was among the first metals that humans employed. Thus, the copper pollution of the world’s water resources is escalating, posing a significant threat to human health and aquatic ecosystems. It is crucial to develop detection technology that is both low-cost and feasible, as well as ultra-selective and sensitive. This study explored the use of the NH₂-Xxx-His motif-derived peptide from phage display technology for ultra-selective Cu²⁺ detection. Various Cu-binding M13 phage clones were isolated, and their affinity and cross-reactivity for different metal ions were determined. A detailed analysis of the amino acid sequence of the unique Cu-binding peptides was employed. For the development of an optical chemosensor, a peptide with an NH₂-Xxx-His motif was selected. The dansyl group was incorporated during solid-phase peptide synthesis, and fluorescence detection assays were employed. The efficacy of the Cu²⁺-binding peptide was verified through spectroscopic measurements. In summary, we developed a highly selective and sensitive fluorescent chemosensor for Cu²⁺ detection based on a peptide sequence from a phage display library that carries the N-terminal Xxx-His motif. Full article

Amino acids and peptides are readily available biomolecules and can function as chiral ligands for transition metal catalysis. An example is the copper complex catalyzed 1,4-addition of dialkylzinc to acyclic enones, which employs peptide ligands. This review provides a dataset of amino acids and peptides reported in the literature proving to be effective ligands for metal-centered catalysts. Several parameters were highlighted, including amino acid combination, metal atoms, carboxyl and amino protecting groups, modification of natural amino acids, and the mechanism of catalysis. Along with analyzing physical-chemical properties, the SMILES representation for each amino acid and/or peptide was generated and made available online, providing an easy-to-use means of training machine learning models. This review offers an opportunity for the development of more efficient peptide ligands for enantioselective metal-centered catalysts. The available online dataset is a reliable manually curated table, it enables the benchmark for comparison of new terminal functional groups. Moreover, the review provides insight into the structures of the more successful peptide ligands and can be used as the foundation for the development of the next generation of peptide-based chiral ligands. Full article

Metal nanoclusters assembled using short peptides as templates exhibit significant potential for development and application in the fields of catalysis and biomedicine, owing to their distinctive electronic structure, favorable optical properties, and biocompatibility. Among them, tripeptides exhibit a simpler structure and greater flexibility, enabling them to readily co-assemble with other functional components to create novel materials with significant application value. They can be assembled with copper ions to synthesize highly efficient luminescent nanoclusters, which can serve as an effective fluorescent probe. Here, we report a method for the synthesis of copper nanoclusters (Cu NCs) using tripeptides as templates, which also act as stabilizers and reducing agents. The synthesis conditions and properties were explored and optimized. Under optimal conditions, the Cu NCs exhibit excellent stability and are strongly fluorescent. The Cu NCs can detect 0.1–1.0 μmol/L of ascorbic acid with a low detection limit of 0.075 μmol/L, demonstrating high sensitivity and offering significant application potential for the trace of ascorbic acid in various substances. It also provides new ideas for the assembly of metal nanoclusters and the construction of fluorescent probe sensing platforms. Full article