TY - JOUR AU - Váradi, Györgyi AU - Bende, Gábor AU - Borics, Attila AU - Dán, Kinga AU - Rákhely, Gábor AU - Tóth, Gábor AU - Galgóczi, László Norbert TI - Rational Design of Antifungal Peptides Based on the γ-Core Motif of a Neosartorya (Aspergillus) fischeri Antifungal Protein to Improve Structural Integrity, Efficacy, and Spectrum JF - ACS OMEGA J2 - ACS OMEGA VL - 9 PY - 2024 IS - 6 SP - 7206 EP - 7214 PG - 9 SN - 2470-1343 DO - 10.1021/acsomega.3c09377 UR - https://m2.mtmt.hu/api/publication/34627084 ID - 34627084 N1 - Funding Agency and Grant Number: , Nemzeti Kutat?si Fejleszt?si ?s Innov?ci?s Hivatal [TKP2021-EGA-32]; Hungarian National Research, Development, and Innovation OfficeyNKFIH [FK 134343]; Hungarian National Research Development and Innovation OfficeyNKFIH; University of Szeged Open Access Fund [6653] Funding text: G.V. and G.K.T. were supported by the TKP2021-EGA-32 fund of the Hungarian National Research, Development, and Innovation OfficeyNKFIH. The present work of L.G. was financed by the Hungarian National Research Development and Innovation OfficeyNKFIH, FK 134343 project. The open-access publishing was supported by the University of Szeged Open Access Fund; grant number: 6653. LA - English DB - MTMT ER - TY - JOUR AU - Dinh, Hoa AU - Kovács, Zsuzsanna AU - Kis, Merse AU - Kupecz, Klaudia AU - Sejben, Anita AU - Szűcs, Gergő AU - Márványkövi, Fanni AU - Siska, Andrea AU - Freiwan, Marah AU - Pósa, Szonja Polett AU - Galla, Zsolt AU - Ibos, Katalin Eszter AU - Bodnár, Éva AU - Lauber, Gülsüm Yilmaz AU - Goncalves, Ana Isabel Antunes AU - Acar, Eylem AU - Kriston, András AU - Kovács, Ferenc AU - Horváth, Péter AU - Bozsó, Zsolt AU - Tóth, Gábor AU - Földesi, Imre AU - Monostori, Péter AU - Cserni, Gábor AU - Podesser, Bruno K. AU - Lehoczki, Andrea Marianna AU - Pokreisz, Peter AU - Kiss, Attila AU - Dux, László AU - Csabafi, Krisztina AU - Sárközy, Márta TI - Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 IS - 2 SP - 2463 EP - 2488 PG - 26 SN - 2509-2715 DO - 10.1007/s11357-023-01017-8 UR - https://m2.mtmt.hu/api/publication/34395398 ID - 34395398 N1 - Department of Biochemistry and Interdisciplinary Centre of Excellence, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, 6720, Hungary Department of Biochemistry, Bach Mai Hospital, Hanoi, 100000, Viet Nam Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, 6720, Hungary Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, 6720, Hungary Department of Laboratory Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, 6720, Hungary Metabolic and Newborn Screening Laboratory, Department of Pediatrics, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, 6720, Hungary Ludwig Boltzmann Institute for Cardiovascular Research at Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, 1090, Austria Synthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, Szeged, 6726, Hungary Single-Cell Technologies Ltd, Szeged, 6726, Hungary Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland Department of Medical Chemistry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, 6720, Hungary Departments of Hematology and Stem Cell Transplantation, South Pest Central Hospital, National Institute of Hematology and Infectious Diseases, Saint Ladislaus Campus, Budapest, Hungary Export Date: 16 April 2024 Correspondence Address: Dux, L.; Department of Biochemistry and Interdisciplinary Centre of Excellence, Hungary; email: dux.laszlo@med.u-szeged.hu Correspondence Address: Sárközy, M.; Department of Biochemistry and Interdisciplinary Centre of Excellence, Hungary; email: martasarkozy@gmail.com AB - The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory ( Il6, Tnf ), fibrosis ( Col1 ), and apoptosis markers ( Bax/Bcl2 ) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle. LA - English DB - MTMT ER - TY - JOUR AU - Fazekas, László Ádám AU - Szabó, Balázs AU - Szegeczki, Vince AU - Fillér, Csaba AU - Varga , Ádám AU - Godó, Zoltán Attila AU - Tóth, Gábor AU - Reglődi, Dóra AU - Juhász, Tamás AU - Németh, Norbert TI - Impact Assessment of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Hemostatic Sponge on Vascular Anastomosis Regeneration in Rats JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 23 PG - 24 SN - 1661-6596 DO - 10.3390/ijms242316695 UR - https://m2.mtmt.hu/api/publication/34444233 ID - 34444233 N1 - Export Date: 3 April 2024 AB - The proper regeneration of vessel anastomoses in microvascular surgery is crucial for surgical safety. Pituitary adenylate cyclase-activating polypeptide (PACAP) can aid healing by decreasing inflammation, apoptosis and oxidative stress. In addition to hematological and hemorheological tests, we examined the biomechanical and histological features of vascular anastomoses with or without PACAP addition and/or using a hemostatic sponge (HS). End-to-end anastomoses were established on the right femoral arteries of rats. On the 21st postoperative day, femoral arteries were surgically removed for evaluation of tensile strength and for histological and molecular biological examination. Effects of PACAP were also investigated in tissue culture in vitro to avoid the effects of PACAP degrading enzymes. Surgical trauma and PACAP absorption altered laboratory parameters; most notably, the erythrocyte deformability decreased. Arterial wall thickness showed a reduction in the presence of HS, which was compensated by PACAP in both the tunica media and adventitia in vivo. The administration of PACAP elevated these parameters in vitro. In conclusion, the application of the neuropeptide augmented elastin expression while HS reduced it, but no significant alterations were detected in collagen type I expression. Elasticity and tensile strength increased in the PACAP group, while it decreased in the HS decreased. Their combined use was beneficial for vascular regeneration. LA - English DB - MTMT ER - TY - JOUR AU - Ugocsai, Melinda AU - Bársony, Anett AU - Varga, Réka A. AU - Gajda, Ámos AU - Vida, Noémi AU - Lajkó, Norbert AU - Rónaszéki, Benedek AU - Tóth, Gábor AU - Boros, Mihály AU - Érces, Dániel AU - Varga, Gabriella TI - Conjugation with Tris Decreases the Risk of Ketoprofen-Induced Mucosal Damage and Reduces Inflammation-Associated Methane Production in a Rat Model of Colitis JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 9 PG - 17 SN - 1999-4923 DO - 10.3390/pharmaceutics15092329 UR - https://m2.mtmt.hu/api/publication/34145694 ID - 34145694 N1 - ISSN:1999-4923 AB - We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments. LA - English DB - MTMT ER - TY - JOUR AU - Patkó, Evelin Viktória AU - Szabó, Edina AU - Váczy, Alexandra AU - Molitor, Dorottya AU - Tari, Eniko AU - Li, Lina AU - Csutak, Adrienne AU - Tóth, Gábor AU - Reglődi, Dóra AU - Atlasz, Tamás TI - Protective Effects of Pituitary Adenylate-Cyclase-Activating Polypeptide on Retinal Vasculature and Molecular Responses in a Rat Model of Moderate Glaucoma JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 17 PG - 14 SN - 1661-6596 DO - 10.3390/ijms241713256 UR - https://m2.mtmt.hu/api/publication/34117220 ID - 34117220 N1 - Export Date: 3 April 2024 AB - Despite the high probability of glaucoma-related blindness, its cause is not fully understood and there is no efficient therapeutic strategy for neuroprotection. Vascular factors have been suggested to play an important role in glaucoma development and progression. Previously, we have proven the neuroprotective effects of pituitary adenylate-cyclase-activating polypeptide (PACAP) eye drops in an inducible, microbeads model in rats that is able to reproduce many clinically relevant features of human glaucoma. In the present study, we examined the potential protective effects of PACAP1-38 on the retinal vasculature and the molecular changes in hypoxia. Ocular hypertension was induced by injection of microbeads into the anterior chamber, while control rats received PBS. PACAP dissolved in vehicle (1 µg/drop) or vehicle treatment was started one day after the injections for four weeks three times a day. Retinal degeneration was assessed with optical coherence tomography (OCT), and vascular and molecular changes were assessed by immunofluorescence labeling. HIF1-α and VEGF-A protein levels were measured by Western blot. OCT images proved severe retinal degeneration in the glaucomatous group, while PACAP1-38 eye drops had a retinoprotective effect. Vascular parameters were deteriorated and molecular analysis suggested hypoxic conditions in glaucoma. PACAP treatment exerted a positive effect against these alterations. In summary, PACAP could prevent the severe damage to the retina and its vasculature induced by ocular hypertension in a microbeads model. LA - English DB - MTMT ER - TY - JOUR AU - Váradi, Györgyi AU - Kele, Zoltán AU - Czajlik, András AU - Borics, Attila AU - Bende, Gábor AU - Papp, Csaba Gergő AU - Rákhely, Gábor AU - Tóth, Gábor AU - Batta, Gyula AU - Galgóczi, László Norbert TI - Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2 JF - PROTEIN SCIENCE J2 - PROTEIN SCI VL - 32 PY - 2023 IS - 7 PG - 13 SN - 0961-8368 DO - 10.1002/pro.4692 UR - https://m2.mtmt.hu/api/publication/34043893 ID - 34043893 N1 - Department of Medical Chemistry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary Department of Biochemistry, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary Laboratory of Chemical Biology, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary Department of Biotechnology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary MTA-SZTE Biomimetic Systems Research Group, University of Szeged, Szeged, Hungary Fungal Genomics and Evolution Lab, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary Export Date: 11 August 2023 CODEN: PRCIE Correspondence Address: Váradi, G.; Department of Medical Chemistry, Dóm tér 8, Hungary; email: varadi.gyorgyi@med.u-szeged.hu Correspondence Address: Galgóczy, L.; Department of Biotechnology, Közép fasor 52, Hungary; email: galgoczi@bio.u-szeged.hu Chemicals/CAS: disulfide, 16734-12-6; Antifungal Agents; Disulfides AB - As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond-stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Aspergillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity. However, in the lack of tryptic and chymotryptic proteolytic sites in the ACNCPNNCK sequence, the determination of the disulfide linkage pattern of NFAP2 is not easy with traditional mass spectrometry-based methods. According to in silico predictions working with a preliminary nuclear magnetic resonance (NMR) solution structure, two disulfide isomers of NFAP2 (abbacc and abbcac) were possible. Both were chemically synthesized; and comparative reversed-phase high-performance liquid chromatography, electronic circular dichroism and NMR spectroscopy analyses, and antifungal susceptibility and efficacy tests indicated that the abbcac is the native pattern. This knowledge allowed rational modification of NAFP2 to improve the antifungal efficacy and spectrum through the modulation of the evolutionarily conserved gamma-core region, which is responsible for the activity of several antimicrobial peptides. Disruption of the steric structure of NFAP2 upon gamma-core modification led to the conclusions that this motif may affect the formation of the biologically active three-dimensional structure, and that the gamma-core modulation is not an efficient tool to improve the antifungal efficacy or to change the antifungal spectrum of NFAP2. LA - English DB - MTMT ER - TY - JOUR AU - Sebák, Fanni AU - Szolomájer, János AU - Papp, Nándor AU - Tóth, Gábor AU - Bodor, Andrea TI - Proline cis/trans Isomerization in Intrinsically Disordered Proteins and Peptides JF - FRONTIERS IN BIOSCIENCE-LANDMARK J2 - FRONT BIOSCI-LANDMARK VL - 28 PY - 2023 IS - 6 PG - 8 SN - 2768-6701 DO - 10.31083/j.fbl2806127 UR - https://m2.mtmt.hu/api/publication/34043118 ID - 34043118 N1 - Analytical and BioNMR Laboratory, Institute of Chemistry, Eötvös Loránd University, Budapest, 1117, Hungary Department of Medical Chemistry, University of Szeged, Szeged, 6720, Hungary Hevesy György PhD School of Chemistry, Eötvös Loránd University, Budapest, 1117, Hungary Export Date: 28 July 2023 Correspondence Address: Bodor, A.; Analytical and BioNMR Laboratory, Hungary; email: andrea.bodor@ttk.elte.hu Chemicals/CAS: proline, 147-85-3, 7005-20-1; Intrinsically Disordered Proteins; Peptides; Proline LA - English DB - MTMT ER - TY - JOUR AU - Szűcs, Mária AU - Tóth, Gábor TI - A 80 éves Penke Botond köszöntése JF - MAGYAR KÉMIKUSOK LAPJA J2 - MAGY KEM LAP VL - 78 PY - 2023 IS - 3 SP - 95 SN - 0025-0163 UR - https://m2.mtmt.hu/api/publication/33773509 ID - 33773509 LA - Hungarian DB - MTMT ER - TY - CONF AU - Hilda, Vass AU - Váradi, Györgyi AU - Kele, Zoltán AU - Gábor, Rákhely AU - Poór, Péter AU - Tóth, Gábor AU - Galgóczi, László Norbert AU - Tóth, Liliána TI - Biocontrol ability of rationally designed peptide derivatives of a novel Solanum lycopersicum L. antifungal defensin T2 - 16th European Conference on Fungal Genetics: Programme & Abstracts PB - Universität Innsbruck C1 - Innsbruck PY - 2023 SP - 478 EP - 479 PG - 2 UR - https://m2.mtmt.hu/api/publication/33748284 ID - 33748284 LA - English DB - MTMT ER - TY - JOUR AU - Váradi, Györgyi AU - Batta, Gyula AU - Galgóczi, László Norbert AU - Hajdu, Dorottya Zsuzsanna AU - Fizil, Ádám AU - Czajlik, András AU - Virágh, Máté AU - Kele, Zoltán AU - Meyer, Vera AU - Jung, Sascha AU - Marx, Florentine AU - Tóth, Gábor TI - Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP JF - JOURNAL OF NATURAL PRODUCTS J2 - J NAT PROD VL - 86 PY - 2023 IS - 4 SP - 782 EP - 790 PG - 9 SN - 0163-3864 DO - 10.1021/acs.jnatprod.2c00954 UR - https://m2.mtmt.hu/api/publication/33676645 ID - 33676645 N1 - Funding Agency and Grant Number: Hungarian National Research, Development [TKP2021-EGA-32]; Innovation Office-NKFIH; Hungarian National Research, Development and Innovation Office-NKFIH [FK 134343]; Austrian Science Fund [392923329]; Deutsche Forschungsgemeinschaft (DFG); [I1644-B20] Funding text: We thank D. Bratschun-Khan for her technical assistance. G.V. and G.K.T. were supported by the TKP2021-EGA-32 fund of the Hungarian National Research, Development, and Innovation Office-NKFIH, and L.G. was financed by the Hungarian National Research, Development and Innovation Office-NKFIH, FK 134343 project. This work was financed by the Austrian Science Fund (FWF I1644-B20) to F.M. and by the Deutsche Forschungsgemeinschaft (DFG, GRK2473 Bioactive Peptides project number 392923329) to S.J. and V.M. AB - Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation. The native protein was synthesized via oxidative folding with uniform protection for cysteine thiols. AFP's biological activity depends heavily on the pattern of natural disulfide bonds. Enzymatic digestion and MS analysis provide proof for interlocking disulfide topology (abcdabcd) that was previously assumed. With this knowledge, a semi-orthogonal thiol protection method was designed. By following this strategy, out of a possible 105, only 6 disulfide isomers formed and 1 of them proved to be identical with the native protein. This approach allows the synthesis of analogs for examining structure-activity relationships and, thus, preparing AFP variants with higher antifungal activity. LA - English DB - MTMT ER -