@article{MTMT:34043894, title = {Light-Fueled Primitive Replication and Selection in Biomimetic Chemical Systems}, url = {https://m2.mtmt.hu/api/publication/34043894}, author = {Bartus, Éva and Tököli, Attila and Mag, Beáta Zsófia and Bajcsi, Áron and Kecskeméti, Gábor and Wéber, Edit and Kele, Zoltán and Fenteany, Gabriel and Martinek, Tamás}, doi = {10.1021/jacs.3c03597}, journal-iso = {J AM CHEM SOC}, journal = {JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, volume = {145}, unique-id = {34043894}, issn = {0002-7863}, abstract = {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.}, keywords = {PEPTIDES; DRIVEN}, year = {2023}, eissn = {1520-5126}, pages = {13371-13383}, orcid-numbers = {Bartus, Éva/0000-0001-9976-6978; Tököli, Attila/0000-0001-8413-3182; Kecskeméti, Gábor/0000-0002-5584-6869; Wéber, Edit/0000-0002-5904-0619; Kele, Zoltán/0000-0002-4401-0302; Fenteany, Gabriel/0000-0001-7407-2195; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:33712712, title = {Structural Adaptation of the Single-Stranded DNA-Binding Protein C-Terminal to DNA Metabolizing Partners Guides Inhibitor Design}, url = {https://m2.mtmt.hu/api/publication/33712712}, author = {Tököli, Attila and Bodnár, Brigitta and Bogár, Ferenc and Paragi, Gábor and Hetényi, Anasztázia and Bartus, Éva and Wéber, Edit and Hegedüs, Zsófia and Szabó, Zoltán and Kecskeméti, Gábor and Szakonyi, Gerda and Martinek, Tamás}, doi = {10.3390/pharmaceutics15041032}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {15}, unique-id = {33712712}, issn = {1999-4923}, abstract = {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.}, year = {2023}, eissn = {1999-4923}, orcid-numbers = {Tököli, Attila/0000-0001-8413-3182; Bogár, Ferenc/0000-0002-0611-1452; Paragi, Gábor/0000-0001-5408-1748; Hetényi, Anasztázia/0000-0001-8080-6992; Bartus, Éva/0000-0001-9976-6978; Wéber, Edit/0000-0002-5904-0619; Hegedüs, Zsófia/0000-0002-5546-8167; Szabó, Zoltán/0000-0001-8278-8038; Kecskeméti, Gábor/0000-0002-5584-6869; Szakonyi, Gerda/0000-0002-4366-4283; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:33547706, title = {Soluplus® promotes efficient transport of meloxicam to the central nervous system via nasal administration}, url = {https://m2.mtmt.hu/api/publication/33547706}, author = {Sipos, Bence and Bella, Zsolt and Gróf, Ilona and Veszelka, Szilvia and Deli, Mária Anna and Szűcs, Kálmán Ferenc and Sztojkov-Ivanov, Anita and Ducza, Eszter and Gáspár, Róbert and Kecskeméti, Gábor and Janáky, Tamás and Volk, Balázs and Budai-Szűcs, Mária and Ambrus, Rita and Révész, Piroska and Pannonhalminé Csóka, Ildikó and Katona, Gábor}, doi = {10.1016/j.ijpharm.2023.122594}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {632}, unique-id = {33547706}, issn = {0378-5173}, year = {2023}, eissn = {1873-3476}, orcid-numbers = {Sipos, Bence/0000-0002-0131-4728; Deli, Mária Anna/0000-0001-6084-6524; Gáspár, Róbert/0000-0002-1571-7579; Kecskeméti, Gábor/0000-0002-5584-6869; Janáky, Tamás/0000-0002-6466-8283; Volk, Balázs/0000-0002-2019-1874; Budai-Szűcs, Mária/0000-0001-5187-5702; Révész, Piroska/0000-0002-5336-6052; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781; Katona, Gábor/0000-0003-1564-4813} } @mastersthesis{MTMT:34111150, title = {Quantitative proteomic analysis: from data-independent acquisition to targeted measurements [Kvantitatív proteomikai analízisek: az adatfüggetlen adatgyűjtéstől a célzott mérésekig]}, url = {https://m2.mtmt.hu/api/publication/34111150}, author = {Kecskeméti, Gábor}, doi = {10.14232/phd.11445}, publisher = {Universití of Szeged}, unique-id = {34111150}, year = {2022}, orcid-numbers = {Kecskeméti, Gábor/0000-0002-5584-6869} } @article{MTMT:33046603, title = {An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods}, url = {https://m2.mtmt.hu/api/publication/33046603}, author = {Kecskeméti, Gábor and Tóth-Molnár, Edit and Janáky, Tamás and Szabó, Zoltán}, doi = {10.3390/ijms23158647}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33046603}, issn = {1661-6596}, abstract = {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.}, keywords = {Mass spectrometry; proteomics; LC-MS; tear; data independent analysis}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Kecskeméti, Gábor/0000-0002-5584-6869; Tóth-Molnár, Edit/0000-0001-7989-1616; Janáky, Tamás/0000-0002-6466-8283; Szabó, Zoltán/0000-0001-8278-8038} } @CONFERENCE{MTMT:32475125, title = {Quality by Design based formulation of intranasal meloxicam containing human serum albumin nanoparticles}, url = {https://m2.mtmt.hu/api/publication/32475125}, author = {Katona, Gábor and Balogh, György Tibor and Dargó, Gergő and Gáspár, Róbert and Márki, Árpád and Ducza, Eszter and Sztojkov-Ivanov, Anita and Tömösi, Ferenc and Kecskeméti, Gábor and Janáky, Tamás and Kiss, Tamás and Ambrus, Rita and Pallagi, Edina and Révész, Piroska and Pannonhalminé Csóka, Ildikó}, booktitle = {13th Central European Symposium on Pharmaceutical Technology}, unique-id = {32475125}, year = {2021}, pages = {71-71}, orcid-numbers = {Katona, Gábor/0000-0003-1564-4813; Balogh, György Tibor/0000-0003-3347-1880; Dargó, Gergő/0000-0002-1141-8379; Gáspár, Róbert/0000-0002-1571-7579; Márki, Árpád/0000-0002-6056-8891; Tömösi, Ferenc/0000-0002-6657-5777; Kecskeméti, Gábor/0000-0002-5584-6869; Janáky, Tamás/0000-0002-6466-8283; Kiss, Tamás/0000-0003-0011-0501; Révész, Piroska/0000-0002-5336-6052; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @article{MTMT:32382697, title = {Kynurenic acid and kynurenine aminotransferase are potential biomarkers of early neurological improvement after thrombolytic therapy : a pilot study}, url = {https://m2.mtmt.hu/api/publication/32382697}, author = {Annus, Ádám and Tömösi, Ferenc and Rárosi, Ferenc and Huszár Lászlóné Fehér, Evelin and Janáky, Tamás and Kecskeméti, Gábor and Toldi, József and Klivényi, Péter and Sztriha, László Krisztián and Vécsei, László}, doi = {10.17219/acem/141646}, journal-iso = {ADV CLIN EXP MED}, journal = {ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE}, volume = {30}, unique-id = {32382697}, issn = {1899-5276}, abstract = {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.}, keywords = {thrombolysis; KYNURENINE; ischemic stroke; ACUTE STROKE; biomarker}, year = {2021}, eissn = {2451-2680}, pages = {1225-1232}, orcid-numbers = {Annus, Ádám/0000-0003-0498-6578; Tömösi, Ferenc/0000-0002-6657-5777; Rárosi, Ferenc/0000-0002-1014-9242; Huszár Lászlóné Fehér, Evelin/0000-0003-2564-3937; Janáky, Tamás/0000-0002-6466-8283; Kecskeméti, Gábor/0000-0002-5584-6869; Toldi, József/0000-0001-7355-0503; Klivényi, Péter/0000-0002-5389-3266; Vécsei, László/0000-0001-8037-3672} } @article{MTMT:32082174, title = {Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period}, url = {https://m2.mtmt.hu/api/publication/32082174}, author = {Tuka, Bernadett and Nyári, Aliz and Cseh, Edina Katalin and Körtési, Tamás and Veréb, Dániel and Tömösi, Ferenc and Kecskeméti, Gábor and Janáky, Tamás and Tajti, János and Vécsei, László}, doi = {10.1186/s10194-021-01239-1}, journal-iso = {J HEADACHE PAIN}, journal = {JOURNAL OF HEADACHE AND PAIN}, volume = {22}, unique-id = {32082174}, issn = {1129-2369}, year = {2021}, eissn = {1129-2377}, orcid-numbers = {Tuka, Bernadett/0000-0002-1410-4666; Körtési, Tamás/0000-0002-8535-5067; Veréb, Dániel/0000-0003-2077-5252; Tömösi, Ferenc/0000-0002-6657-5777; Kecskeméti, Gábor/0000-0002-5584-6869; Janáky, Tamás/0000-0002-6466-8283; Tajti, János/0000-0003-0857-5266; Vécsei, László/0000-0001-8037-3672} } @article{MTMT:32009571, title = {Design, synthesis and biological evaluation of novel estrone phosphonates as high affinity organic anion-transporting polypeptide 2B1 (OATP2B1) inhibitors}, url = {https://m2.mtmt.hu/api/publication/32009571}, author = {Jójárt, Rebeka and Laczkó-Rigó, Réka and Klement, Máté and Kőhl, Gabriella and Kecskeméti, Gábor and Laczka, Csilla and Mernyák, Erzsébet}, doi = {10.1016/j.bioorg.2021.104914}, journal-iso = {BIOORG CHEM}, journal = {BIOORGANIC CHEMISTRY}, volume = {112}, unique-id = {32009571}, issn = {0045-2068}, year = {2021}, eissn = {1090-2120}, orcid-numbers = {Kecskeméti, Gábor/0000-0002-5584-6869; Mernyák, Erzsébet/0000-0003-4494-1817} } @article{MTMT:31646463, title = {Inhibition of ABCG2/BCRP-mediated transport–correlation analysis of various expression systems and probe substrates}, url = {https://m2.mtmt.hu/api/publication/31646463}, author = {Sáfár, Zsolt and Kecskeméti, Gábor and Molnár, Judit and Kurunczi, Anita and Szabó, Zoltán and Janáky, Tamás and Kis, Emese and Krajcsi, Péter}, doi = {10.1016/j.ejps.2020.105593}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {156}, unique-id = {31646463}, issn = {0928-0987}, abstract = {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.}, keywords = {ABCG2; Vesicular transport; BCRP; HEK293-BCRP; substrate-dependent inhibition}, year = {2021}, eissn = {1879-0720}, orcid-numbers = {Kecskeméti, Gábor/0000-0002-5584-6869; Szabó, Zoltán/0000-0001-8278-8038; Janáky, Tamás/0000-0002-6466-8283; Krajcsi, Péter/0000-0002-4450-5954} }