Kata Horvati

@ttk.hun-ren.hu

Institute of Materials and Environmental Chemistry
HUN-REN Research Centre for Natural Sciences



              

https://researchid.co/khorvati
7

Scopus Publications

192

Scholar Citations

3

Scholar h-index

6

Scholar i10-index

Scopus Publications

  • Supramolecular Complexes of Ultrashort Cationic Lipopeptides with Cyclodextrins: Improved Selectivity and Therapeutic Potential
    Chiara Bellini, Unai Atxabal, Szilvia Bősze, Orsolya Dobay, Andrea Horváth, Imola Cs. Szigyártó, Tamás Beke‐Somfai, Jesús Jiménez‐Barbero, István Puskás, and Kata Horváti
    Wiley
    ABSTRACTIn the last decade, the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develop resistance. However, lipopeptides often show undesired cytotoxicity due to their non‐selective membrane disruptive effect, and their limited aqueous solubility represents a matter of concern from a pharmaceutical point of view. This study demonstrates a panel of ultrashort cationic lipopeptides (USCLs) consisting of a tetrapeptide (L1), originated from buforin II, coupled with saturated fatty acids of different lengths. Our results highlight that the 16‐carbon fatty acid lipopeptide (Pal‐L1) exhibits relevant antibacterial activity against multiresistant Staphylococcus aureus strain. However, the formation of heterogenic aggregates in cell culture medium and toxic effects on human cells were also observed. Pal‐L1 formulation with the randomly methylated α‐cyclodextrin (RAMEA) and the sulfobutylether‐β‐cyclodextrin (SBECD) has resulted in a production of ultralow‐sized molecular dispersion systems and reduced lipopeptide toxicity without compromising its antimicrobial activity. With titration 1H‐NMR, 2D NMR experiments, together with molecular dynamics simulations, we described the size, structure, stoichiometry, and dissociation constant of the supramolecular complexes. Interactions of neutral and negatively charged model liposomes with Pal‐L1 lipopeptide in the presence or absence of cyclodextrins serve an explanation for the membrane selectivity, and based on the results, we proposed a potential mechanism of action for the Pal‐L1+cyclodextrin complexes on different biological membranes. Overall, our model characterization points out that cyclodextrin formulation improves the therapeutical applicability of lipopeptides.

  • Optimizing lipopeptide bioactivity: The impact of non-ionic surfactant dressing
    Ágnes Ábrahám, Gergő Gyulai, Judith Mihály, Andrea Horváth, Orsolya Dobay, Zoltán Varga, Éva Kiss, and Kata Horváti
    Elsevier BV

  • In situ captured antibacterial action of membrane-incising peptide lamellae
    Kamal el Battioui, Sohini Chakraborty, András Wacha, Dániel Molnár, Mayra Quemé-Peña, Imola Cs. Szigyártó, Csenge Lilla Szabó, Andrea Bodor, Kata Horváti, Gergő Gyulai,et al.
    Springer Science and Business Media LLC
    AbstractDeveloping unique mechanisms of action are essential to combat the growing issue of antimicrobial resistance. Supramolecular assemblies combining the improved biostability of non-natural compounds with the complex membrane-attacking mechanisms of natural peptides are promising alternatives to conventional antibiotics. However, for such compounds the direct visual insight on antibacterial action is still lacking. Here we employ a design strategy focusing on an inducible assembly mechanism and utilized electron microscopy (EM) to follow the formation of supramolecular structures of lysine-rich heterochiral β3-peptides, termed lamellin-2K and lamellin-3K, triggered by bacterial cell surface lipopolysaccharides. Combined molecular dynamics simulations, EM and bacterial assays confirmed that the phosphate-induced conformational change on these lamellins led to the formation of striped lamellae capable of incising the cell envelope of Gram-negative bacteria thereby exerting antibacterial activity. Our findings also provide a mechanistic link for membrane-targeting agents depicting the antibiotic mechanism derived from the in-situ formation of active supramolecules.

  • Hyperbranched polyglycerol grafted poly(N,N-diethylacrylamide) thermoresponsive copolymers as biocompatible, highly efficient encapsulation and sustained release systems of curcumin
    György Kasza, Ákos Fábián, Dóra Fecske, Attila Kardos, Róbert Mészáros, Kata Horváti, and Béla Iván
    Elsevier BV

  • Bidirectional Allosteric Coupling between PIP<inf>2</inf> Binding and the Pore of the Oncochannel TRPV6
    Christina Humer, Tamara Radiskovic, Kata Horváti, Sonja Lindinger, Klaus Groschner, Christoph Romanin, and Carmen Höglinger
    MDPI AG
    The epithelial ion channel TRPV6 plays a pivotal role in calcium homeostasis. Channel function is intricately regulated at different stages, involving the lipid phosphatidylinositol-4,5-bisphosphate (PIP2). Given that dysregulation of TRPV6 is associated with various diseases, including different types of cancer, there is a compelling need for its pharmacological targeting. Structural studies provide insights on how TRPV6 is affected by different inhibitors, with some binding to sites else occupied by lipids. These include the small molecule cis-22a, which, however, also binds to and thereby blocks the pore. By combining calcium imaging, electrophysiology and optogenetics, we identified residues within the pore and the lipid binding site that are relevant for regulation by cis-22a and PIP2 in a bidirectional manner. Yet, mutation of the cytosolic pore exit reduced inhibition by cis-22a but preserved sensitivity to PIP2 depletion. Our data underscore allosteric communication between the lipid binding site and the pore and vice versa for most sites along the pore.

  • Effective nanoparticulate-type encapsulation delivery system for hydrophilic proteins and peptides
    Flavio Massignan, Gergő Gyulai, Kata Horváti, Szilvia Bősze, and Éva Kiss
    Department of Polymer Engineering, Scientific Society of Mechanical Engineering

  • Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection
    Chiara Bellini, Emil Vergara, Fruzsina Bencs, Kinga Fodor, Szilvia Bősze, Denis Krivić, Bernadett Bacsa, Sára Eszter Surguta, József Tóvári, Rajko Reljic,et al.
    American Chemical Society (ACS)
    The complex immunopathology ofMycobacterium tuberculosis(Mtb) is one of the main challenges in developing a novel vaccine against this pathogen, particularly regarding eliciting protection against both active and latent stages. Multistage vaccines, which contain antigens expressed in both phases, represent a promising strategy for addressing this issue, as testified by the tuberculosis vaccine clinical pipeline. Given this approach, we designed and characterized a multistage peptide-based vaccine platform containing CD4+ and CD8+ T cell epitopes previously validated for inducing a relevant T cell response against Mtb. After preliminary screening, CFP10 (32–39), GlfT2 (4–12), HBHA (185–194), and PPE15 (1–15) were selected as promising candidates, and we proved that the PM1 pool of these peptides triggered a T cell response in Mtb-sensitized human peripheral blood mononuclear cells (PBMCs). Taking advantage of the use of thiol-maleimide chemoselective ligation, we synthesized a multiepitope conjugate (Ac-CGHP). Our results showed a structure–activity relationship between the conjugation and a higher tendency to fold and assume an ordered secondary structure. Moreover, the palmitoylated conjugate (Pal-CGHP) comprising the same peptide antigens was associated with an enhanced cellular uptake in human and murine antigen-presenting cells and a better immunogenicity profile. Immunization study, conducted in BALB/c mice, showed that Pal-CGHP induced a significantly higher T cell proliferation and production of IFNγ and TNFα over PM1 formulated in the Sigma Adjuvant System.

  • Arylnaphthalene Lignans with Anti-SARS-CoV-2 and Antiproliferative Activities from the Underground Organs of Linum austriacum and Linum perenne
    Gergő Tóth, Kata Horváti, Márta Kraszni, Tim Ausbüttel, Bernadett Pályi, Zoltán Kis, Zoltán Mucsi, Gábor M. Kovács, Szilvia Bősze, and Imre Boldizsár
    American Chemical Society (ACS)
    Diphyllin (1) and justicidin B (2) are arylnaphthalene lignans with antiviral and antiproliferative effects. Compound 1 is also known as an effective inhibitor of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To evaluate the in vitro antiviral and cytotoxic potency of both lignans in SARS-CoV-2 -infected cells and various cancer cell lines, respectively, 1 and 2 were isolated from the underground organs of Linum austriacum and Linum perenne. Two previously undescribed arylnaphthalene lignans, denominated linadiacin A and B (3 and 4), were also isolated and identified. In acidic media, 3 was converted by a two-step reaction into 2 via the intermediate 4. Optimum acid treatment conditions were determined to isolate lignans by one-step preparative high-performance liquid chromatography (HPLC). The results of the conversion, HPLC-tandem mass spectrometry, nuclear magnetic resonance spectroscopy, and molecular modeling studies allowed complete structure analysis. Compounds 1 and 2 were the most effective against SARS-CoV-2 with a 3-log reduction in the viral copy number at a 12.5 μM concentration. Ten human cancer cell lines showed sensitivity to at least one of the isolated lignans.

  • Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
    Tünde Juhász, Mayra Quemé-Peña, Bence Kővágó, Judith Mihály, Maria Ricci, Kata Horváti, Szilvia Bősze, Ferenc Zsila, and Tamás Beke-Somfai
    Springer Science and Business Media LLC
    AbstractIn the emerging era of antimicrobial resistance, the susceptibility to co-infections of patients suffering from either acquired or inherited hemolytic disorders can lead to dramatic increase in mortality rates. Closely related, heme liberated during hemolysis is one of the major sources of iron, which is vital for both host and invading microorganisms. While recent intensive research in the field has demonstrated that heme exerts diverse local effects including impairment of immune cells functions, it is almost completely unknown how it may compromise key molecules of our innate immune system, such as antimicrobial host defense peptides (HDPs). Since HDPs hold great promise as natural therapeutic agents against antibiotic-resistant microbes, understanding the effects that may modulate their action in microbial infection is crucial. Here we explore how hemin can interact directly with selected HDPs and influence their structure and membrane activity. It is revealed that induced helical folding, large assembly formation, and altered membrane activity is promoted by hemin. However, these effects showed variations depending mainly on peptide selectivity toward charged lipids, and the affinity of the peptide and hemin to lipid bilayers. Hemin-peptide complexes are sought to form semi-folded co-assemblies, which are present even with model membranes resembling mammalian or bacterial lipid compositions. In vitro cell-based toxicity assays supported that toxic effects of HDPs could be attenuated due to their assembly formation. These results are in line with our previous findings on peptide-lipid-small molecule systems suggesting that small molecules present in the complex in vivo milieu can regulate HDP function. Inversely, diverse effects of endogenous compounds could also be manipulated by HDPs.

  • Novel Assay Platform to Evaluate Intracellular Killing of Mycobacterium tuberculosis: In Vitro and In Vivo Validation
    Kata Horváti, Kinga Fodor, Bernadett Pályi, Judit Henczkó, Gyula Balka, Gergő Gyulai, Éva Kiss, Beáta Biri-Kovács, Zsuzsanna Senoner, and Szilvia Bősze
    Frontiers Media SA
    One of the main hallmarks of tuberculosis (TB) is the ability of the causative agent to transform into a stage of dormancy and the capability of long persistence in the host phagocytes. It is believed that approximately one-third of the population of the world is latently infected with Mycobacterium tuberculosis (Mtb), and 5%–10% of these individuals can develop clinical manifestations of active TB even decades after the initial infection. In this latent, intracellular form, the bacillus is shielded by an extremely robust cell wall and becomes phenotypically resistant to most antituberculars. Therefore, there is a clear rationale to develop novel compounds or carrier-conjugated constructs of existing drugs that are effective against the intracellular form of the bacilli. In this paper, we describe an experimental road map to define optimal candidates against intracellular Mtb and potential compounds effective in the therapy of latent TB. To validate our approach, isoniazid, a first-line antitubercular drug was employed, which is active against extracellular Mtb in the submicromolar range, but ineffective against the intracellular form of the bacteria. Cationic peptide conjugates of isoniazid were synthesized and employed to study the host-directed drug delivery. To measure the intracellular killing activity of the compounds, Mtb-infected MonoMac-6 human monocytic cells were utilized. We have assessed the antitubercular activity, cytotoxicity, membrane interactions in combination with internalization efficacy, localization, and penetration ability on interface and tissue-mimicking 3D models. Based on these in vitro data, most active compounds were further evaluated in vivo in a murine model of TB. Intraperitoneal infectious route was employed to induce a course of slowly progressive and systemic disease. The well-being of the animals, monitored by the body weight, allows a prolonged experimental setup and provides a great opportunity to test the long-term activity of the drug candidates. Having shown the great potency of this simple and suitable experimental design for antimicrobial research, the proposed novel assay platform could be used in the future to develop further innovative and highly effective antituberculars.

  • Tissue-specific accumulation and isomerization of valuable phenylethanoid glycosides from Plantago and Forsythia plants
    Moritz Zürn, Gergő Tóth, Tim Ausbüttel, Zoltán Mucsi, Kata Horváti, Szilvia Bősze, Magdolna Sütöri-Diószegi, Bernadett Pályi, Zoltán Kis, Béla Noszál,et al.
    MDPI AG
    A comparative phytochemical study on the phenylethanoid glycoside (PhEG) composition of the underground organs of three Plantago species (P. lanceolata, P. major, and P. media) and that of the fruit wall and seed parts of Forsythia suspensa and F. europaea fruits was performed. The leaves of these Forsythia species and six cultivars of the hybrid F. × intermedia were also analyzed, demonstrating the tissue-specific accumulation and decomposition of PhEGs. Our analyses confirmed the significance of selected tissues as new and abundant sources of these valuable natural compounds. The optimized heat treatment of tissues containing high amounts of the PhEG plantamajoside (PM) or forsythoside A (FA), which was performed in distilled water, resulted in their characteristic isomerizations. In addition to PM and FA, high amounts of the isomerization products could also be isolated after heat treatment. The isomerization mechanisms were elucidated by molecular modeling, and the structures of PhEGs were identified by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HR-MS) techniques, also confirming the possibility of discriminating regioisomeric PhEGs by tandem MS. The PhEGs showed no cytostatic activity in non-human primate Vero E6 cells, supporting their safe use as natural medicines and allowing their antiviral potency to be tested.

  • Comparison of the efficacy of two novel antitubercular agents in free and liposome-encapsulated formulations
    Nikoletta Kósa, Ádám Zolcsák, István Voszka, Gabriella Csík, Kata Horváti, Lilla Horváth, Szilvia Bősze, and Levente Herenyi
    MDPI AG
    Tuberculosis is one of the top ten causes of death worldwide, and due to the appearance of drug-resistant strains, the development of new antituberculotic agents is a pressing challenge. Employing an in silico docking method, two coumaran (2,3-dihydrobenzofuran) derivatives—TB501 and TB515—were determined, with promising in vitro antimycobacterial activity. To enhance their effectiveness and reduce their cytotoxicity, we used liposomal drug carrier systems. Two types of small unilamellar vesicles (SUV) were prepared: multicomponent pH-sensitive stealth liposome (SUVmixed) and monocomponent conventional liposome. The long-term stability of our vesicles was obtained by the examination of particle size distribution with dynamic light scattering. Encapsulation efficiency (EE) of the two drugs was determined from absorption spectra before and after size exclusion chromatography. Cellular uptake and cytotoxicity were determined on human MonoMac-6 cells by flow cytometry. The antitubercular effect was characterized by the enumeration of colony-forming units on Mycobacterium tuberculosis H37Rv infected MonoMac-6 cultures. We found that SUVmixed + TB515 has the best long-term stability. TB515 has much higher EE in both types of SUVs. Cellular uptake for native TB501 is extremely low, but if it is encapsulated in SUVmixed it appreciably increases; in the case of TB515, quasi total uptake is accessible. It is concluded that SUVmixed + TB501 seems to be the most efficacious antitubercular formulation given the presented experiments; to find the most promising antituberculotic formulation for therapy further in vivo investigations are needed.

  • Cost-Effective Flow Peptide Synthesis: Metamorphosis of HPLC
    Viktor Farkas, Kristóf Ferentzi, Kata Horváti, and András Perczel
    American Chemical Society (ACS)
    We present the further development and fine-tuning of an efficient, economic (≤3 equivalents of activated amino acid ), and environmentally friendly (6 mL organic waste/cycle) procedure for peptide...

  • Old Polyanionic Drug Suramin Suppresses Detrimental Cytotoxicity of the Host Defense Peptide LL-37
    Mayra Quemé-Peña, Maria Ricci, Tünde Juhász, Kata Horváti, Szilvia Bősze, Beáta Biri-Kovács, Bálint Szeder, Ferenc Zsila, and Tamás Beke-Somfai
    American Chemical Society (ACS)

  • Recent advances in the development of protein-and peptide-based subunit vaccines against tuberculosis
    Chiara Bellini and Kata Horváti
    MDPI AG
    The World Health Organization (WHO) herald of the “End TB Strategy” has defined goals and targets for tuberculosis prevention, care, and control to end the global tuberculosis endemic. The emergence of drug resistance and the relative dreadful consequences in treatment outcome has led to increased awareness on immunization against Mycobacterium tuberculosis (Mtb). However, the proven limited efficacy of Bacillus Calmette-Guérin (BCG), the only licensed vaccine against Mtb, has highlighted the need for alternative vaccines. In this review, we seek to give an overview of Mtb infection and failure of BCG to control it. Afterward, we focus on the protein- and peptide-based subunit vaccine subtype, examining the advantages and drawbacks of using this design approach. Finally, we explore the features of subunit vaccine candidates currently in pre-clinical and clinical evaluation, including the antigen repertoire, the exploited adjuvanted delivery systems, as well as the spawned immune response.

  • Drug conjugation induced modulation of structural and membrane interaction features of cationic cell-permeable peptides
    Edit Pári, Kata Horváti, Szilvia Bősze, Beáta Biri-Kovács, Bálint Szeder, Ferenc Zsila, and Éva Kiss
    MDPI AG
    Cell-penetrating peptides might have great potential for enhancing the therapeutic effect of drug molecules against such dangerous pathogens as Mycobacterium tuberculosis (Mtb), which causes a major health problem worldwide. A set of cationic cell-penetration peptides with various hydrophobicity were selected and synthesized as drug carrier of isoniazid (INH), a first-line antibacterial agent against tuberculosis. Molecular interactions between the peptides and their INH-conjugates with cell-membrane-forming lipid layers composed of DPPC and mycolic acid (a characteristic component of Mtb cell wall) were evaluated, using the Langmuir balance technique. Secondary structure of the INH conjugates was analyzed and compared to that of the native peptides by circular dichroism spectroscopic experiments performed in aqueous and membrane mimetic environment. A correlation was found between the conjugation induced conformational and membrane affinity changes of the INH–peptide conjugates. The degree and mode of interaction were also characterized by AFM imaging of penetrated lipid layers. In vitro biological evaluation was performed with Penetratin and Transportan conjugates. Results showed similar internalization rate into EBC-1 human squamous cell carcinoma, but markedly different subcellular localization and activity on intracellular Mtb.

  • Anionic food color tartrazine enhances antibacterial efficacy of histatin-derived peptide DHVAR4 by fine-tuning its membrane activity
    Maria Ricci, Kata Horváti, Tünde Juhász, Imola Szigyártó, György Török, Fanni Sebák, Andrea Bodor, László Homolya, Judit Henczkó, Bernadett Pályi,et al.
    Cambridge University Press (CUP)
    AbstractHere it is demonstrated how some anionic food additives commonly used in our diet, such as tartrazine (TZ), bind to DHVAR4, an antimicrobial peptide (AMP) derived from oral host defense peptides, resulting in significantly fostered toxic activity against both Gram-positive and Gram-negative bacteria, but not against mammalian cells. Biophysical studies on the DHVAR4–TZ interaction indicate that initially large, positively charged aggregates are formed, but in the presence of lipid bilayers, they rather associate with the membrane surface. In contrast to synergistic effects observed for mixed antibacterial compounds, this is a principally different mechanism, where TZ directly acts on the membrane-associated AMP promoting its biologically active helical conformation. Model vesicle studies show that compared to dye-free DHVAR4, peptide–TZ complexes are more prone to form H-bonds with the phosphate ester moiety of the bilayer head-group region resulting in more controlled bilayer fusion mechanism and concerted severe cell damage. AMPs are considered as promising compounds to combat formidable antibiotic-resistant bacterial infections; however, we know very little on their in vivo actions, especially on how they interact with other chemical agents. The current example illustrates how food dyes can modulate AMP activity, which is hoped to inspire improved therapies against microbial infections in the alimentary tract. Results also imply that the structure and function of natural AMPs could be manipulated by small compounds, which may also offer a new strategic concept for the future design of peptide-based antimicrobials.

  • Galls of European Fraxinus trees as new and abundant sources of valuable phenylethanoid and coumarin glycosides
    Moritz Zürn, Gergő Tóth, Márta Kraszni, Anna Sólyomváry, Zoltán Mucsi, Ruth Deme, Balázs Rózsa, Blanka Fodor, Ibolya Molnár-Perl, Kata Horváti,et al.
    Elsevier BV

  • A convenient synthetic method to improve immunogenicity of mycobacterium tuberculosis related T-cell epitope peptides
    Kata Horváti, Bernadett Pályi, Judit Henczkó, Gyula Balka, Eleonóra Szabó, Viktor Farkas, Beáta Biri-Kovács, Bálint Szeder, and Kinga Fodor
    MDPI AG
    Epitopes from different proteins expressed by Mycobacterium tuberculosis (Rv1886c, Rv0341, Rv3873) were selected based on previously reported antigenic properties. Relatively short linear T-cell epitope peptides generally have unordered structure, limited immunogenicity, and low in vivo stability. Therefore, they rely on proper formulation and on the addition of adjuvants. Here we report a convenient synthetic route to induce a more potent immune response by the formation of a trivalent conjugate in spatial arrangement. Chemical and structural characterization of the vaccine conjugates was followed by the study of cellular uptake and localization. Immune response was assayed by the measurement of splenocyte proliferation and cytokine production, while vaccine efficacy was studied in a murine model of tuberculosis. The conjugate showed higher tendency to fold and increased internalization rate into professional antigen presenting cells compared to free epitopes. Cellular uptake was further improved by the incorporation of a palmitoyl group to the conjugate and the resulted pal-A(P)I derivative possessed an internalization rate 10 times higher than the free epitope peptides. Vaccination of CB6F1 mice with free peptides resulted in low T-cell response. In contrast, significantly higher T-cell proliferation with prominent expression of IFN-γ, IL-2, and IL-10 cytokines was measured for the palmitoylated conjugate. Furthermore, the pal-A(P)I conjugate showed relevant vaccine efficacy against Mycobacterium tuberculosis infection.

  • Chemical structure and in vitro cellular uptake of luminescent carbon quantum dots prepared by solvothermal and microwave assisted techniques
    Gergő Gyulai, Fatima Ouanzi, Imre Bertóti, Miklós Mohai, Tamás Kolonits, Kata Horváti, and Szilvia Bősze
    Elsevier BV

  • Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 with the Polysulfonated Drug Suramin: A Step Closer to in Vivo Complexity
    Mayra Quemé‐Peña, Tünde Juhász, Judith Mihály, Imola Cs. Szigyártó, Kata Horváti, Szilvia Bősze, Judit Henczkó, Bernadett Pályi, Csaba Németh, Zoltán Varga,et al.
    Wiley
    AbstractAntimicrobial peptides (AMPs) kill bacteria by targeting their membranes through various mechanisms involving peptide assembly, often coupled with disorder‐to‐order structural transition. However, for several AMPs, similar conformational changes in cases in which small organic compounds of both endogenous and exogenous origin have induced folded peptide conformations have recently been reported. Thus, the function of AMPs and of natural host defence peptides can be significantly affected by the local complex molecular environment in vivo; nonetheless, this area is hardly explored. To address the relevance of such interactions with regard to structure and function, we have tested the effects of the therapeutic drug suramin on the membrane activity and antibacterial efficiency of CM15, a potent hybrid AMP. The results provided insight into a dynamic system in which peptide interaction with lipid bilayers is interfered with by the competitive binding of CM15 to suramin, resulting in an equilibrium dependent on peptide‐to‐drug ratio and vesicle surface charge. In vitro bacterial tests showed that when CM15⋅suramin complex formation dominates over membrane binding, antimicrobial activity is abolished. On the basis of this case study, it is proposed that small‐molecule secondary structure regulators can modify AMP function and that this should be considered and could potentially be exploited in future development of AMP‐based antimicrobial agents.

  • A road map for prioritizing warheads for cysteine targeting covalent inhibitors
    Péter Ábrányi-Balogh, László Petri, Tímea Imre, Péter Szijj, Andrea Scarpino, Martina Hrast, Ana Mitrović, Urša Pečar Fonovič, Krisztina Németh, Hélène Barreteau,et al.
    Elsevier BV


  • Surface Layer Modification of Poly(d, l -lactic- co-glycolic acid) Nanoparticles with Targeting Peptide: A Convenient Synthetic Route for Pluronic F127-Tuftsin Conjugate
    Kata Horváti, Gergő Gyulai, Antal Csámpai, János Rohonczy, Éva Kiss, and Szilvia Bősze
    American Chemical Society (ACS)
    Nanoparticles consisting of biodegradable poly(d,l-lactic- co-glycolic acid) (PLGA) are promising carriers for drug molecules to improve the treatment of tuberculosis. Surface modifiers, such as Pluronic F127, are essential for biocompatibility and for the protection against particle aggregation. This study demonstrates a successful approach to conjugate Pluronic F127 coated PLGA nanoparticles with Tuftsin, which has been reported as a macrophage-targeting peptide. Transformation of Pluronic F127 hydroxyl groups-which have limited reactivity-into aldehyde groups provide a convenient way to bind aminooxy-peptide derivatives in a one-step reaction. We have also investigated that this change has no effect on the physicochemical properties of the nanoparticles. Our data showed that coating nanoparticles with Pluronic-Tuftsin conjugate markedly increased the internalization rate and the intracellular activity of the encapsulated drug candidate against Mycobacterium tuberculosis. By employing this approach, a large variety of peptide targeted PLGA nanoparticles can be designed for drug delivery.

  • Hemin and bile pigments are the secondary structure regulators of intrinsically disordered antimicrobial peptides
    Ferenc Zsila, Tünde Juhász, Szilvia Bősze, Kata Horváti, and Tamás Beke‐Somfai
    Wiley
    AbstractThe interaction of protoporphyrin compounds of human origin with the major bee venom component melittin (26 a.a., Z +6) and its hybrid derivative (CM15, 15 a.a., Z +6) were studied by a combination of various spectroscopic methods. Throughout a two‐state, concentration‐dependent process, hemin and its metabolites (biliverdin, bilirubin, bilirubin ditaurate) increase the parallel β‐sheet content of the natively unfolded melittin, suggesting the oligomerization of the peptide chains. In contrast, α‐helix promoting effect was observed with the also disordered but more cationic CM15. According to fluorescence quenching experiments, the sole Trp residue of melittin is the key player during the binding, in the vicinity of which the first pigment molecule is accommodated presumably making indole‐porphyrin π‐π stacking interaction. As circular dichroism titration data suggest, cooperative association of additional ligands subsequently occurs, resulting in multimeric complexes with an apparent dissociation constant ranged from 20 to 65 μM. Spectroscopic measurements conducted with the bilirubin catabolite urobilin and stercobilin refer to the requirement of intact dipyrrinone moieties for inducing secondary structure transformations. The binding topography of porphyrin rings on a model parallel β‐sheet motif was evaluated by absorption spectroscopy and computational modeling showing a slipped‐cofacial binding mode responsible for the red shift and hypochromism of the Soret band. Our results may aid to recognize porphyrin‐responsive binding motifs of biologically relevant, intrinsically disordered peptides and proteins, where transient conformations play a vital role in their functions.

RECENT SCHOLAR PUBLICATIONS

  • Supramolecular Complexes of Ultrashort Cationic Lipopeptides with Cyclodextrins: Improved Selectivity and Therapeutic Potential
    C Bellini, U Atxabal, S Bősze, O Dobay, A Horvth, IC Szigyrt, ...
    Aggregate, e741 2025

  • In situ captured antibacterial action of membrane-incising peptide lamellae
    K El Battioui, S Chakraborty, A Wacha, D Molnr, M Quem-Pea, ...
    Nature Communications 15 (1), 3424 2024

  • Bidirectional Allosteric Coupling between PIP2 Binding and the Pore of the Oncochannel TRPV6
    C Humer, T Radiskovic, K Horvti, S Lindinger, K Groschner, C Romanin, ...
    International Journal of Molecular Sciences 25 (1), 618 2024

  • Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection
    C Bellini, E Vergara, F Bencs, K Fodor, S Bősze, D Krivić, B Bacsa, ...
    Bioconjugate Chemistry 34 (10), 1738-1753 2023

  • Arylnaphthalene Lignans with Anti-SARS-CoV-2 and Antiproliferative Activities from the Underground Organs of Linum austriacum and Linum perenne
    G Toth, K Horvti, M Kraszni, T Ausbuttel, B Plyi, Z Kis, Z Mucsi, ...
    Journal of Natural Products 86 (4), 672-682 2023

  • Novel Assay Platform to Evaluate Intracellular Killing of Mycobacterium tuberculosis: In Vitro and In Vivo Validation
    K Horvti, K Fodor, B Plyi, J Henczk, G Balka, G Gyulai, Kiss, ...
    Frontiers in Immunology 12, 750496 2021

  • Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
    T Juhsz, M Quem-Pea, B Kővg, J Mihly, M Ricci, K Horvati, ...
    Scientific Reports 11 (1), 18328 2021

  • Mitigation of the Cathelicidin Peptide LL-37 Cytotoxicity Induced by Interaction with the Polysulfonated Drug Suramin
    M Quem-Pea, M Ricci, T Juhsz, S Bősze, B Biri-Kovcs, B Szeder, ...
    MDPI 2021

  • Tissue-Specific Accumulation and Isomerization of Valuable Phenylethanoid Glycosides from Plantago and Forsythia Plants
    M Zrn, G Tth, T Ausbttel, Z Mucsi, K Horvati, S Bősze, ...
    International Journal of Molecular Sciences 22 (8), 3880 2021

  • Comparison of the efficacy of two novel antitubercular agents in free and liposome-encapsulated formulations
    N Ksa, Zolcsk, I Voszka, G Csk, K Horvati, L Horvath, S Bősze, ...
    International Journal of Molecular Sciences 22 (5), 2457 2021

  • Cost-effective flow peptide synthesis: metamorphosis of HPLC
    V Farkas, K Ferentzi, K Horvati, A Perczel
    Organic Process Research & Development 25 (2), 182-191 2021

  • Recent advances in the development of protein-and peptide-based subunit vaccines against tuberculosis
    C Bellini, K Horvati
    Cells 9 (12), 2673 2020

  • Old polyanionic drug suramin suppresses detrimental cytotoxicity of the host defense peptide LL-37
    M Quemé-Peña, M Ricci, T Juhász, K Horváti, S Bősze, B Biri-Kovács, ...
    ACS Pharmacology & Translational Science 4 (1), 155-167 2020

  • Drug conjugation induced modulation of structural and membrane interaction features of cationic cell-permeable peptides
    E Pri, K Horvati, S Bősze, B Biri-Kovacs, B Szeder, F Zsila, E Kiss
    International Journal of Molecular Sciences 21 (6), 2197 2020

  • Anionic food color tartrazine enhances antibacterial efficacy of histatin-derived peptide DHVAR4 by fine-tuning its membrane activity
    M Ricci, T Juhsz, I Szigyrt, G Trk, F Sebk, A Bodor, L Homolya, ...
    Quarterly reviews of biophysics 53, e5 2020

  • Galls of European Fraxinus trees as new and abundant sources of valuable phenylethanoid and coumarin glycosides
    M Zrn, G Tth, M Kraszni, A Slyomvry, Z Mucsi, R Deme, B Rzsa, ...
    Industrial Crops and Products 139, 111517 2019

  • A Convenient Synthetic Method to Improve Immunogenicity of Mycobacterium tuberculosis Related T-Cell Epitope Peptides
    K Horvati, B Plyi, J Henczko, G Balka, E Szabo, V Farkas, B Biri-Kovacs, ...
    Vaccines 7 (3), 101 2019

  • Chemical structure and in vitro cellular uptake of luminescent carbon quantum dots prepared by solvothermal and microwave assisted techniques
    G Gyulai, F Ouanzi, I Bertti, M Mohai, T Kolonits, S Bősze
    Journal of colloid and interface science 549, 150-161 2019

  • Manipulating active structure and function of cationic antimicrobial peptide CM15 with the polysulfonated drug suramin: a step closer to in vivo complexity
    M Quem‐Pea, T Juhsz, J Mihly, I Cs. Szigyrt, K Horvti, S Bősze, ...
    ChemBioChem 20 (12), 1578-1590 2019

  • A road map for prioritizing warheads for cysteine targeting covalent inhibitors
    P Abranyi-Balogh, L Petri, T Imre, P Szijj, A Scarpino, M Hrast, A Mitrović, ...
    European journal of medicinal chemistry 160, 94-107 2018

MOST CITED SCHOLAR PUBLICATIONS

  • Solid-phase synthesis of difficult peptide sequences at elevated temperatures: a critical comparison of microwave and conventional heating technologies
    B Bacsa, K Horvati, S Bosze, F Andreae, CO Kappe
    The Journal of organic chemistry 73 (19), 7532-7542 2008
    Citations: 226

  • A road map for prioritizing warheads for cysteine targeting covalent inhibitors
    P Abranyi-Balogh, L Petri, T Imre, P Szijj, A Scarpino, M Hrast, A Mitrović, ...
    European journal of medicinal chemistry 160, 94-107 2018
    Citations: 130

  • New fluorine-containing hydrazones active against MDR-tuberculosis
    E Vavřkov, S Polanc, M Kočevar, S Bősze, J Stolařkov, K Vvrov, ...
    European journal of medicinal chemistry 46 (10), 4937-4945 2011
    Citations: 80

  • New series of isoniazid hydrazones linked with electron-withdrawing substituents
    E Vavřkov, S Polanc, M Kočevar, J Košmrlj, S Bősze, J Stolařkov, ...
    European journal of medicinal chemistry 46 (12), 5902-5909 2011
    Citations: 55

  • Nanoparticle encapsulated lipopeptide conjugate of antitubercular drug isoniazid: in vitro intracellular activity and in vivo efficacy in a Guinea pig model of tuberculosis
    K Horvati, B Bacsa, Kiss, G Gyulai, K Fodor, G Balka, M Rusvai, ...
    Bioconjugate chemistry 25 (12), 2260-2268 2014
    Citations: 50

  • New amino acid esters of salicylanilides active against MDR-TB and other microbes
    M Krtk, J Vinšov, V Buchta, S Bsze, J Stolařkov
    European journal of medicinal chemistry 45 (12), 6106-6113 2010
    Citations: 50

  • Chemical structure and in vitro cellular uptake of luminescent carbon quantum dots prepared by solvothermal and microwave assisted techniques
    G Gyulai, F Ouanzi, I Bertti, M Mohai, T Kolonits, S Bősze
    Journal of colloid and interface science 549, 150-161 2019
    Citations: 42

  • Enhanced Cellular Uptake of a New, in Silico Identified Antitubercular Candidate by Peptide Conjugation
    K Horváti, B Bacsa, N Szabó, S Dávid, G Mező, V Grolmusz, B Vértessy, ...
    Bioconjugate chemistry 23 (5), 900-907 2012
    Citations: 41

  • Comparative analysis of internalisation, haemolytic, cytotoxic and antibacterial effect of membrane-active cationic peptides: Aspects of experimental setup
    K Horvti, B Bacsa, T Mlink, N Szab, F Hudecz, F Zsila, S Bősze
    Amino Acids 49, 1053-1067 2017
    Citations: 40

  • Antimycobacterial activity of peptide conjugate of pyridopyrimidine derivative against Mycobacterium tuberculosis in a series of in vitro and in vivo models
    B Bacsa, N Szab, K Fodor, G Balka, M Rusvai, Kiss, G Mező, ...
    Tuberculosis 95, S207-S211 2015
    Citations: 39

  • Tuneable surface modification of PLGA nanoparticles carrying new antitubercular drug candidate
     Kiss, G Gyulai, CB Pnzes, M Idei, K Horvti, B Bacsa, S Bősze
    Colloids and Surfaces A: Physicochemical and Engineering Aspects 458, 178-186 2014
    Citations: 35

  • Peptide conjugates of therapeutically used antitubercular isoniazid—design, synthesis and antimycobacterial effect
    K Horvati, G Mező, N Szabo, F Hudecz, S Bősze
    Journal of Peptide Science: An Official Publication of the European Peptide 2009
    Citations: 35

  • Combating highly resistant emerging pathogen Mycobacterium abscessus and Mycobacterium tuberculosis with novel salicylanilide esters and carbamates
    Z Baranyai, M Krtk, J Vinšov, N Szab, Z Senoner, J Stolařkov, ...
    European journal of medicinal chemistry 101, 692-704 2015
    Citations: 34

  • Recent advances in the development of protein-and peptide-based subunit vaccines against tuberculosis
    C Bellini, K Horvati
    Cells 9 (12), 2673 2020
    Citations: 33

  • Surface Layer Modification of Poly(d,l-lactic-co-glycolic acid) Nanoparticles with Targeting Peptide: A Convenient Synthetic Route for Pluronic F127–Tuftsin
    K Horváti, G Gyulai, A Csámpai, J Rohonczy, E Kiss, S Bősze
    Bioconjugate chemistry 29 (5), 1495-1499 2018
    Citations: 32

  • Nanoencapsulation of antitubercular drug isoniazid and its lipopeptide conjugate
     Kiss, D Schnller, K Pribranska, K Hill, CB Pnzes, K Horvti, S Bősze
    Journal of dispersion science and technology 32 (12), 1728-1734 2011
    Citations: 28

  • Cost-effective flow peptide synthesis: metamorphosis of HPLC
    V Farkas, K Ferentzi, K Horvati, A Perczel
    Organic Process Research & Development 25 (2), 182-191 2021
    Citations: 25

  • Manipulating active structure and function of cationic antimicrobial peptide CM15 with the polysulfonated drug suramin: a step closer to in vivo complexity
    M Quem‐Pea, T Juhsz, J Mihly, I Cs. Szigyrt, K Horvti, S Bősze, ...
    ChemBioChem 20 (12), 1578-1590 2019
    Citations: 25

  • Cytotoxicity decreasing effect and antimycobacterial activity of chitosan conjugated with antituberculotic drugs
    E Vavřkov, J Mandkov, F Trejtnar, S Bsze, J Stolařkov, J Vinšov
    Carbohydrate polymers 83 (4), 1901-1907 2011
    Citations: 22

  • Hemin and bile pigments are the secondary structure regulators of intrinsically disordered antimicrobial peptides
    F Zsila, T Juhsz, S Bősze, K Horvati, T Beke‐Somfai
    Chirality 30 (2), 195-205 2018
    Citations: 21