TY - JOUR AU - Hlogyik, Tamás AU - Laczkó-Rigó, Réka AU - Bakos, Éva AU - Poór, Miklós AU - Kele, Zoltán AU - Laczka, Csilla AU - Mernyák, Erzsébet TI - Synthesis and in vitro photodynamic activity of aza-BODIPY-based photosensitizers JF - ORGANIC & BIOMOLECULAR CHEMISTRY J2 - ORG BIOMOL CHEM VL - 21 PY - 2023 IS - 29 SP - 6018 EP - 6027 PG - 10 SN - 1477-0520 DO - 10.1039/d3ob00699a UR - https://m2.mtmt.hu/api/publication/34067941 ID - 34067941 N1 - * Megosztott szerzőség AB - Aza-BODIPY dyes have recently come to attention owing to their excellent chemical and photophysical properties. In particular, their absorption and emission maxima can efficiently be shifted to the red or even to the NIR spectral region. On this basis, aza-BODIPY derivatives are widely investigated as fluorescent probes or phototherapeutic agents. Here we report the synthesis of a set of novel aza-BODIPY derivatives as potential photosensitizers for use in photodynamic therapy. Triazolyl derivatives were obtained via Cu(I)-catalyzed azide-alkyne cycloaddition as the key step. In vitro photodynamic activities of the newly synthesized compounds were evaluated on the A431 human epidermoid carcinoma cell line. Structural differences influenced the light-induced toxicity of the test compounds markedly. Compared to the initial tetraphenyl aza-BODIPY derivative, the compound bearing two hydrophilic triethylene glycol side chains showed substantial, more than 250-fold, photodynamic activity with no dark toxicity. Our newly synthesized aza-BODIPY derivative, acting in the nanomolar range, might serve as a promising candidate for the design of more active and selective photosensitizers. LA - English DB - MTMT ER - TY - JOUR AU - Bartus, Éva AU - Tököli, Attila AU - Mag, Beáta Zsófia AU - Bajcsi, Áron AU - Kecskeméti, Gábor AU - Wéber, Edit AU - Kele, Zoltán AU - Fenteany, Gabriel AU - Martinek, Tamás TI - Light-Fueled Primitive Replication and Selection in Biomimetic Chemical Systems JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 145 PY - 2023 IS - 24 SP - 13371 EP - 13383 PG - 13 SN - 0002-7863 DO - 10.1021/jacs.3c03597 UR - https://m2.mtmt.hu/api/publication/34043894 ID - 34043894 N1 - Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary ELKH-SZTE Biomimetic Systems Research Group, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Institute of Genetics, Biological Research Centre, Temesvári krt. 62, Szeged, H-6726, Hungary Cited By :2 Export Date: 17 April 2024 CODEN: JACSA Correspondence Address: Martinek, T.A.; Department of Medical Chemistry, Dóm tér 8, Hungary; email: martinek.tamas@med.u-szeged.hu AB - The concept of chemically evolvable replicators is centralto abiogenesis.Chemical evolvability requires three essential components: energy-harvestingmechanisms for nonequilibrium dissipation, kinetically asymmetricreplication and decomposition pathways, and structure-dependent selectivetemplating in the autocatalytic cycles. We observed a UVA light-fueledchemical system displaying sequence-dependent replication and replicatordecomposition. The system was constructed with primitive peptidicfoldamer components. The photocatalytic formation-recombinationcycle of thiyl radicals was coupled with the molecular recognitionsteps in the replication cycles. Thiyl radical-mediated chain reactionwas responsible for the replicator death mechanism. The competingand kinetically asymmetric replication and decomposition processesled to light intensity-dependent selection far from equilibrium. Here,we show that this system can dynamically adapt to energy influx andseeding. The results highlight that mimicking chemical evolution isfeasible with primitive building blocks and simple chemical reactions. 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 - 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 - TY - CHAP AU - Dán, Kinga AU - Kele, Zoltán AU - Váradi, Györgyi AU - Tóth, Liliána AU - Tóth, Gábor AU - Rákhely, Gábor AU - Galgóczi, László Norbert TI - Intracellular protein targets of Neosartorya (Aspergillus) fischeri antifungal protein 2 in Candida albicans T2 - FEMS Conference on Microbiology in association with Serbian Society of Microbiology PB - Serbian Society of Microbiology CY - Belgrád SN - 9788691489786 PY - 2022 SP - 808 EP - 809 PG - 2 UR - https://m2.mtmt.hu/api/publication/33250254 ID - 33250254 LA - English DB - MTMT ER - TY - JOUR AU - Szolomájer, János AU - Stráner, Pál AU - Kele, Zoltán AU - Tóth, Gábor AU - Perczel, András TI - Synthesis of the extracellular domain of GLP-1R by chemical and biotechnological approaches JF - RSC ADVANCES J2 - RSC ADV VL - 12 PY - 2022 IS - 37 SP - 24278 EP - 24287 PG - 10 SN - 2046-2069 DO - 10.1039/D2RA02784D UR - https://m2.mtmt.hu/api/publication/33071352 ID - 33071352 N1 - Department of Medical Chemistry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, H-6720, Hungary MTA-ELTE Protein Model. Res. Group and Laboratory of Structural Chemistry and Biology, Pázmány P. stny. 1/A, Budapest, 1117, Hungary Laboratory of Structural Chemistry and Biology, Institute of Chemistry, ELTE Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary MTA-SZTE Biomimetic Research Group, University of Szeged, Szeged, H-6720, Hungary Export Date: 5 April 2023 CODEN: RSCAC Correspondence Address: Tóth, G.K.; Department of Medical Chemistry, Hungary; email: toth.gabor@med.u-szeged.hu Correspondence Address: Perczel, A.; MTA-ELTE Protein Model. Res. Group and Laboratory of Structural Chemistry and Biology, Pázmány P. stny. 1/A, Hungary; email: perczel@chem.elte.hu AB - The extracellular domain of the glucagon-like peptide-1 receptor, GLP-1R, is responsible for the binding of GLP-1, and a handful of additional agonists (such as exenatide, lixisenatide, and liraglutide) used daily for treating type II diabetes mellitus. Lead discovery and optimization, however, require binding studies, which, in turn, necessitate the total synthesis of GLP-1R, comprising 108 residues. A protein domain of 10–15 kDa size could be obtained either by expression in E. coli or by ligating solid-phase peptide synthesis (SPPS)-made fragments. However, direct overexpression fails to give a properly folded protein, as GLP-1R forms an inclusion body, which fails to refold due to improper disulfide pairing. Several bacterial strains, constructs, and fusion partners were probed and it was found that only co-expression with MBP gave a 3D-fold allowing the native disulfide bond pattern formation. Some fusion partners can act as covalently linked or in situ chaperones for guiding the refolding of GLP-1R toward success. Therefore, the bottleneck to preparing GPCR extracellular domains is the correct pairing of the Cys residues. As a proof-of-concept model, nGLP1-R was made by SPPS to form the purified full-length polypeptide chain, subjected to self-guided or spontaneous Cys pairing. However, the formation of correct SS-pairs was lagging behind any protocol in use support, and the bottleneck of large-scale protein production relies on the risky step of proper refolding, which is sometimes possible only if a suitable fusion partner effectively helps and catalysis of the correct disulfide formation. LA - English DB - MTMT ER - TY - JOUR AU - Váradi, Zoltán AU - Paragi, Gábor AU - Kupihár, Zoltán AU - Kele, Zoltán AU - Kovács, Lajos TI - Synthesis of Heterocycles and Nucleosides Forming Higher—Order Structures JF - CHEMISTRY PROCEEDINGS J2 - CHEM PROC VL - 8 PY - 2022 IS - 1 PG - 6 SN - 2673-4583 DO - 10.3390/ecsoc-25-11705 UR - https://m2.mtmt.hu/api/publication/32818711 ID - 32818711 LA - English DB - MTMT ER - TY - JOUR AU - Vágvölgyi, Máté AU - Kocsis, Endre AU - Nové, Márta AU - Szemerédi, Nikoletta AU - Spengler, Gabriella AU - Kele, Zoltán AU - Berkecz, Róbert AU - Gáti, Tamás AU - Tóth, Gábor AU - Hunyadi, Attila TI - Diversity-Oriented Synthesis Catalyzed by Diethylaminosulfur-Trifluoride—Preparation of New Antitumor Ecdysteroid Derivatives JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 7 PG - 18 SN - 1661-6596 DO - 10.3390/ijms23073447 UR - https://m2.mtmt.hu/api/publication/32770194 ID - 32770194 N1 - Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, H-6720, Hungary Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Szeged, H-6725, Hungary Department of Medical Chemistry, University of Szeged, Szeged, H-6720, Hungary Institute of Pharmaceutical Analysis, University of Szeged, Szeged, H-6720, Hungary Servier Research Institute of Medicinal Chemistry (SRIMC), Budapest, H-1031, Hungary NMR Group, Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Budapest, H-1111, Hungary Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, H-6720, Hungary Export Date: 9 June 2023 Correspondence Address: Tóth, G.; NMR Group, Hungary; email: drtothgabor@t-online.hu Correspondence Address: Hunyadi, A.; Institute of Pharmacognosy, Hungary; email: hunyadi.a@pharmacognosy.hu Chemicals/CAS: cyclopropane, 75-19-4; doxorubicin, 23214-92-8, 25316-40-9; ecdysterone, 5289-74-7; diethylamine, 109-89-7, 660-68-4; fluorine, 7782-41-4; Diethylamines; diethylaminosulfur trifluoride; Ecdysteroids; Fluorine Manufacturers: Teva, Hungary Funding details: GINOP-2.3.2-15-2016-00012 Funding details: FEIF/646-4/2021-ITM_SZERZ Funding details: UNKP-21-4-SZTE-281 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K-134704, TKP2021-EGA-32 Funding details: National Research, Development and Innovation Office Funding text 1: Funding: This research was funded by the National Research, Development and Innovation Office, Hungary (NKFIH; K-134704 and TKP2021-EGA-32 by the Ministry of Innovation and Technology of Hungary), and the Economic Development and Innovation Operative Program GINOP-2.3.2-15-2016-00012, with the support of the Szeged Scientists Academy under the sponsorship of the Hungarian Ministry of Innovation and Technology (FEIF/646-4/2021-ITM_SZERZ). M.V. was supported by the New National Excellence Program of the Ministry of Human Capacities, Hungary (UNKP-21-4-SZTE-281). AB - Fluorine represents a privileged building block in pharmaceutical chemistry. Diethylaminosulfur-trifluoride (DAST) is a reagent commonly used for replacement of alcoholic hydroxyl groups with fluorine and is also known to catalyze water elimination and cyclic Beckmann-rearrangement type reactions. In this work we aimed to use DAST for diversity-oriented semisynthetic transformation of natural products bearing multiple hydroxyl groups to prepare new bioactive compounds. Four ecdysteroids, including a new constituent of Cyanotis arachnoidea, were selected as starting materials for DAST-catalyzed transformations. The newly prepared compounds represented combinations of various structural changes DAST was known to catalyze, and a unique cyclopropane ring closure that was found for the first time. Several compounds demonstrated in vitro antitumor properties. A new 17-N-acetylecdysteroid (13) exerted potent antiproliferative activity and no cytotoxicity on drug susceptible and multi-drug resistant mouse T-cell lymphoma cells. Further, compound 13 acted in significant synergism with doxorubicin without detectable direct ABCB1 inhibition. Our results demonstrate that DAST is a versatile tool for diversity-oriented synthesis to expand chemical space towards new bioactive compounds. LA - English DB - MTMT ER - TY - JOUR AU - Böszörményi, Éva AU - Kása, Zsolt AU - Varga, Gábor AU - Kele, Zoltán AU - Kutus, Bence AU - Peintler, Gábor AU - Pálinkó, István AU - Sipos, Pál Miklós TI - Formation of mono- and binuclear complexes of Nd3+ with d-gluconate ions in hyperalkaline solutions – Composition, equilibria and structure JF - JOURNAL OF MOLECULAR LIQUIDS J2 - J MOL LIQ VL - 346 PY - 2022 PG - 9 SN - 0167-7322 DO - 10.1016/j.molliq.2021.117047 UR - https://m2.mtmt.hu/api/publication/32132785 ID - 32132785 LA - English DB - MTMT ER -