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 - Tököli, Attila AU - Bodnár, Brigitta AU - Bogár, Ferenc AU - Paragi, Gábor AU - Hetényi, Anasztázia AU - Bartus, Éva AU - Wéber, Edit AU - Hegedüs, Zsófia AU - Szabó, Zoltán AU - Kecskeméti, Gábor AU - Szakonyi, Gerda AU - Martinek, Tamás TI - Structural Adaptation of the Single-Stranded DNA-Binding Protein C-Terminal to DNA Metabolizing Partners Guides Inhibitor Design JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 4 PG - 17 SN - 1999-4923 DO - 10.3390/pharmaceutics15041032 UR - https://m2.mtmt.hu/api/publication/33712712 ID - 33712712 N1 - Department of Medical Chemistry, University of Szeged, Szeged, H6720, Hungary ELKH-SZTE Biomimetic Systems Research Group, Eötvös Loránd Research Network (ELKH), Szeged, H6720, Hungary Institute of Physics, University of Pécs, Pécs, H7624, Hungary Department of Theoretical Physics, University of Szeged, Szeged, H6720, Hungary Institute of Pharmaceutical Analysis, University of Szeged, Szeged, H6720, Hungary Export Date: 8 September 2023 Correspondence Address: Martinek, T.A.; Department of Medical Chemistry, Hungary; email: martinek.tamas@med.u-szeged.hu AB - Single-stranded DNA-binding protein (SSB) is a bacterial interaction hub and an appealing target for antimicrobial therapy. Understanding the structural adaptation of the disordered SSB C-terminus (SSB-Ct) to DNA metabolizing enzymes (e.g., ExoI and RecO) is essential for designing high-affinity SSB mimetic inhibitors. Molecular dynamics simulations revealed the transient interactions of SSB-Ct with two hot spots on ExoI and RecO. The residual flexibility of the peptide–protein complexes allows adaptive molecular recognition. Scanning with non-canonical amino acids revealed that modifications at both termini of SSB-Ct could increase the affinity, supporting the two-hot-spot binding model. Combining unnatural amino acid substitutions on both segments of the peptide resulted in enthalpy-enhanced affinity, accompanied by enthalpy–entropy compensation, as determined by isothermal calorimetry. NMR data and molecular modeling confirmed the reduced flexibility of the improved affinity complexes. Our results highlight that the SSB-Ct mimetics bind to the DNA metabolizing targets through the hot spots, interacting with both of segments of the ligands. LA - English DB - MTMT ER - TY - JOUR AU - Sipos, Bence AU - Bella, Zsolt AU - Gróf, Ilona AU - Veszelka, Szilvia AU - Deli, Mária Anna AU - Szűcs, Kálmán Ferenc AU - Sztojkov-Ivanov, Anita AU - Ducza, Eszter AU - Gáspár, Róbert AU - Kecskeméti, Gábor AU - Janáky, Tamás AU - Volk, Balázs AU - Budai-Szűcs, Mária AU - Ambrus, Rita AU - Révész, Piroska AU - Pannonhalminé Csóka, Ildikó AU - Katona, Gábor TI - Soluplus® promotes efficient transport of meloxicam to the central nervous system via nasal administration JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 632 PY - 2023 PG - 11 SN - 0378-5173 DO - 10.1016/j.ijpharm.2023.122594 UR - https://m2.mtmt.hu/api/publication/33547706 ID - 33547706 LA - English DB - MTMT ER - TY - THES AU - Kecskeméti, Gábor TI - Quantitative proteomic analysis: from data-independent acquisition to targeted measurements [Kvantitatív proteomikai analízisek: az adatfüggetlen adatgyűjtéstől a célzott mérésekig] PB - Szegedi Tudományegyetem PY - 2022 SP - 66 DO - 10.14232/phd.11445 UR - https://m2.mtmt.hu/api/publication/34111150 ID - 34111150 LA - English DB - MTMT ER - TY - JOUR AU - Kecskeméti, Gábor AU - Tóth-Molnár, Edit AU - Janáky, Tamás AU - Szabó, Zoltán TI - An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 15 PG - 20 SN - 1661-6596 DO - 10.3390/ijms23158647 UR - https://m2.mtmt.hu/api/publication/33046603 ID - 33046603 AB - Tear samples are considered in recent publications as easily, noninvasively collectible information sources for precision medicine. Their complex composition may aid the identification of biomarkers and the monitoring of the effectiveness of treatments for the eye and systemic diseases. Sample collection and processing are key steps in any analytical method, especially if subtle personal differences need to be detected. In this work, we evaluate the usability of a novel sample collection technique for human tear samples using phenol red threads (cotton thread treated with the pH indicator phenol red), which are efficiently used to measure tear volume in clinical diagnosis. The low invasiveness and low discomfort to the patients have already been demonstrated, but their applicability for proteomic sample collection has not yet been compared to other methods. We have shown, using various statistical approaches, the qualitative and quantitative differences in proteomic samples collected with this novel and two traditional methods using either glass capillaries or Schirmer’s paper strips. In all parameters studied, the phenol red threads proved to be equally or even more suitable than traditional methods. Based on detectability using different sampling methods, we have classified proteins in tear samples. LA - English DB - MTMT ER - TY - CONF AU - Katona, Gábor AU - Balogh, György Tibor AU - Dargó, Gergő AU - Gáspár, Róbert AU - Márki, Árpád AU - Ducza, Eszter AU - Sztojkov-Ivanov, Anita AU - Tömösi, Ferenc AU - Kecskeméti, Gábor AU - Janáky, Tamás AU - Kiss, Tamás AU - Ambrus, Rita AU - Pallagi, Edina AU - Révész, Piroska AU - Pannonhalminé Csóka, Ildikó ED - Malgorzata, Sznitowska TI - Quality by Design based formulation of intranasal meloxicam containing human serum albumin nanoparticles T2 - 13th Central European Symposium on Pharmaceutical Technology PB - Medical University of Gdansk C1 - Gdansk PY - 2021 SP - 71 EP - 71 PG - 1 UR - https://m2.mtmt.hu/api/publication/32475125 ID - 32475125 LA - English DB - MTMT ER - TY - JOUR AU - Annus, Ádám AU - Tömösi, Ferenc AU - Rárosi, Ferenc AU - Huszár Lászlóné Fehér, Evelin AU - Janáky, Tamás AU - Kecskeméti, Gábor AU - Toldi, József AU - Klivényi, Péter AU - Sztriha, László Krisztián AU - Vécsei, László TI - Kynurenic acid and kynurenine aminotransferase are potential biomarkers of early neurological improvement after thrombolytic therapy : a pilot study JF - ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE J2 - ADV CLIN EXP MED VL - 30 PY - 2021 IS - 12 SP - 1225 EP - 1232 PG - 8 SN - 1899-5276 DO - 10.17219/acem/141646 UR - https://m2.mtmt.hu/api/publication/32382697 ID - 32382697 N1 - Department of Neurology, Albert Szent-Györgyi Health Centre, University of Szeged, Hungary Department of Medical Chemistry, University of Szeged, Hungary Department of Medical Physics and Informatics, University of Szeged, Hungary Department of Physiology, Anatomy and Neuroscience, University of Szeged, Hungary Department of Neurology, King’s College Hospital, London, United Kingdom MTA-SZTE Neuroscience Research Group, Szeged, Hungary Interdisciplinary Excellence Centre, University of Szeged, Hungary Cited By :2 Export Date: 7 March 2024 Correspondence Address: Vécsei, L.; Department of Neurology, Hungary; email: vecsei.laszlo@med.u-szeged.hu AB - Biomarkers for predicting treatment response to thrombolysis in acute ischemic stroke are currently lacking. Both, animal models and clinical studies have provided evidence that the kynurenine (KYN) pathway is activated in ischemic stroke.In our pilot study, we aimed to investigate whether KYN pathway enzymes and metabolites could serve as potential biomarkers for treatment response in the hyperacute phase of ischemic stroke.We included 48 acute ischemic stroke patients who received thrombolysis. Blood samples were taken both before and 12 h after treatment. Concentrations of 11 KYN metabolites were determined using ultra-high-performance liquid chromatography-mass spectrometry. To assess the treatment response, we used early neurological improvement (ENI), calculated as the difference between the admission and discharge National Institutes of Health Stroke Scale (NIHSS) scores. We performed receiver operating characteristic (ROC) analysis for KYN pathway metabolites and enzymes that showed a correlation with ENI.In the samples taken before thrombolysis, significantly lower concentrations of kynurenic acid (KYNA) and kynurenine aminotransferase (KAT) activity were found in patients who had ENI (p = 0.01 and p = 0.002, respectively). According to the ROC analysis, the optimal cut-off value to predict ENI for KYNA was 37.80 nM (sensitivity (SN) 69.2%, specificity (SP) 68.4%) and 0.0127 for KAT activity (SN 92.3%, SP 73.7%).Our research is the first clinical pilot study to analyze changes in the KYN pathway in ischemic stroke patients who received thrombolytic treatment. Based on our results, baseline KYNA concentration and KAT activity could serve as potential biomarkers to predict early treatment response to thrombolysis. LA - English DB - MTMT ER - TY - JOUR AU - Tuka, Bernadett AU - Nyári, Aliz AU - Cseh, Edina Katalin AU - Körtési, Tamás AU - Veréb, Dániel AU - Tömösi, Ferenc AU - Kecskeméti, Gábor AU - Janáky, Tamás AU - Tajti, János AU - Vécsei, László TI - Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period JF - JOURNAL OF HEADACHE AND PAIN J2 - J HEADACHE PAIN VL - 22 PY - 2021 IS - 1 PG - 19 SN - 1129-2369 DO - 10.1186/s10194-021-01239-1 UR - https://m2.mtmt.hu/api/publication/32082174 ID - 32082174 N1 - Funding Agency and Grant Number: MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences -University of Szeged; Hungarian Brain Research Program [KTIA_13_NAP-A-III/9]; University of Szeged Open Access Fund [5108]; TKP2020 Thematic Excellence Program [0 T 204 2939/211, NKFIH-1279-2/2020]; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-19-3]; [EFOP-3.6.3-VEKOP-16-2017-00009] Funding text: This work was supported by the MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences -University of Szeged, the Hungarian Brain Research Program: Grant No. KTIA_13_NAP-A-III/9, University of Szeged Open Access Fund, Grant: 5108. Bernadett Tuka was supported by the TKP2020 Thematic Excellence Program 0 T 204 2939/211, Edina Katalin Cseh and Tamas Kortesi were supported by the UNKP-19-3 New National Excellence Program of the Ministry for Innovation and Technology, Edina Katalin Cseh was supported by the EFOP-3.6.3-VEKOP-16-2017-00009 Program and Laszlo Vecsei was supported by the NKFIH-1279-2/2020 TKP2020 Thematic Excellence Program. LA - English DB - MTMT ER - TY - JOUR AU - Jójárt, Rebeka AU - Laczkó-Rigó, Réka AU - Klement, Máté AU - Kőhl, Gabriella AU - Kecskeméti, Gábor AU - Laczka, Csilla AU - Mernyák, Erzsébet TI - Design, synthesis and biological evaluation of novel estrone phosphonates as high affinity organic anion-transporting polypeptide 2B1 (OATP2B1) inhibitors JF - BIOORGANIC CHEMISTRY J2 - BIOORG CHEM VL - 112 PY - 2021 PG - 12 SN - 0045-2068 DO - 10.1016/j.bioorg.2021.104914 UR - https://m2.mtmt.hu/api/publication/32009571 ID - 32009571 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Drug Resistance Research Group instead of Membrane Protein Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Magyar tudósok körútja 2Budapest H-1117, Hungary Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Export Date: 26 August 2021 LA - English DB - MTMT ER - TY - JOUR AU - Sáfár, Zsolt AU - Kecskeméti, Gábor AU - Molnár, Judit AU - Kurunczi, Anita AU - Szabó, Zoltán AU - Janáky, Tamás AU - Kis, Emese AU - Krajcsi, Péter TI - Inhibition of ABCG2/BCRP-mediated transport–correlation analysis of various expression systems and probe substrates JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 156 PY - 2021 PG - 11 SN - 0928-0987 DO - 10.1016/j.ejps.2020.105593 UR - https://m2.mtmt.hu/api/publication/31646463 ID - 31646463 N1 - Solvo Biotechnology, a Charles River Company, 52 Közép fasor, Szeged, H-6726, Hungary Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Solvo Biotechnology, a Charles River Company, 4-20 Irinyi J str, Budapest, H-1117, Hungary Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter str 50/a, Budapest, H-1083, Hungary Semmelweis University, Faculty of Health Sciences, Vas str 17, Budapest, H-1088, Hungary Cited By :3 Export Date: 12 January 2024 CODEN: EPSCE Correspondence Address: Krajcsi, P.; Solvo Biotechnology, 52 Közép fasor, Hungary; email: krajcsi@solvo.com AB - BCRP / ABCG2 is a key determinant of pharmacokinetics of substrate drugs. Several BCRP substrates and inhibitors are of low passive permeability, and the vesicular transport assay works well in this permeability space. Membranes were prepared from BCRP-HEK293, MCF-7/MX, and baculovirus-infected Sf9 cells with (BCRP-Sf9-HAM), and without (BCRP-Sf9) cholesterol loading. Km values for three substrates - estrone-3-sulfate, sulfasalazine, topotecan - correlated well between the four expression systems. In contrast, a 10-20-fold range in Vmax values was observed, with BCRP-HEK293 membranes possessing the largest dynamic range. IC50 values of the different test systems were similar to each other, with 94.4% of pairwise comparisons being within 3-fold. Substrate dependent inhibition showed somewhat greater variation, as 81.4% of IC50 values in the BCRP-HEK293 membranes were within 3-fold in pairwise comparisons. Overall, BCRP-HEK293 membranes demonstrated the highest activity. The IC50 values showed good concordance but substrate dependent inhibition was observed for some drugs. LA - English DB - MTMT ER -