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 - Simon, Márton AU - Bartus, Éva AU - Mag, Beáta Zsófia AU - Boros, Eszter AU - Roszjár, Lea AU - Gógl, Gergő AU - Travé, Gilles AU - Martinek, Tamás AU - Nyitray, László TI - Promiscuity mapping of the S100 protein family using a high-throughput holdup assay JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 11 SN - 2045-2322 DO - 10.1038/s41598-022-09574-2 UR - https://m2.mtmt.hu/api/publication/32777033 ID - 32777033 N1 - These authors contributed equally: Márton A. Simon and Éva Bartus LA - English DB - MTMT ER - TY - GEN AU - Simon, Márton AU - Bartus, Éva AU - Mag, Beáta Zsófia AU - Boros, Eszter AU - Roszjár, Lea AU - Gógl, Gergő AU - Travé, Gilles AU - Martinek, Tamás AU - Nyitray, László TI - Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay PY - 2020 UR - https://m2.mtmt.hu/api/publication/31867968 ID - 31867968 AB - S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally-occurring S100 partners in the human proteome. Such information will be precious for future drug design of modulators of S100 pathological activities. LA - English DB - MTMT ER - TY - JOUR AU - Tököli, Attila AU - Mag, Beáta Zsófia AU - Bartus, Éva AU - Wéber, Edit AU - Szakonyi, Gerda AU - Simon, Márton AU - Czibula, Ágnes AU - Monostori, Éva AU - Nyitray, László AU - Martinek, Tamás TI - Proteomimetic surface fragments distinguish targets by function JF - CHEMICAL SCIENCE J2 - CHEM SCI VL - 11 PY - 2020 IS - 38 SP - 10390 EP - 10398 PG - 9 SN - 2041-6520 DO - 10.1039/d0sc03525d UR - https://m2.mtmt.hu/api/publication/31598466 ID - 31598466 LA - English DB - MTMT ER - TY - GEN AU - Bartus, Éva AU - Mag, Beáta Zsófia AU - Kecskeméti, Gábor AU - Kele, Zoltán AU - Martinek, Tamás TI - Fénnyel hajtott disszipatív kovalens kémia foldamer ligandumok optimalizálására PY - 2019 UR - https://m2.mtmt.hu/api/publication/31624662 ID - 31624662 N1 - Előadás - II/1. szekció: Peptid szerkezet, peptid analitika LA - Hungarian DB - MTMT ER - TY - THES AU - Bartus, Éva TI - Bottom-up design of foldamers for protein surface recognition PB - Szegedi Tudományegyetem (SZTE) PY - 2019 SP - 52 DO - 10.14232/phd.10208 UR - https://m2.mtmt.hu/api/publication/31269723 ID - 31269723 LA - English DB - MTMT ER - TY - JOUR AU - Bartus, Éva AU - Olajos, Gábor AU - Schuster, Ildikó AU - Bozsó, Zsolt AU - Deli, Mária Anna AU - Veszelka, Szilvia AU - Walter, Fruzsina AU - Datki, Zsolt László AU - Szakonyi, Zsolt AU - Martinek, Tamás AU - Fülöp, Lívia TI - Structural optimization of foldamer-dendrimer conjugates as multivalent agents against the toxic effects of amyloid beta oligomers JF - MOLECULES J2 - MOLECULES VL - 23 ET - 0 PY - 2018 IS - 10 PG - 14 SN - 1420-3049 DO - 10.3390/molecules23102523 UR - https://m2.mtmt.hu/api/publication/30310687 ID - 30310687 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [GINOP-2.2.1-15-2016-00007]; Hungarian Brain Research Program I and II [KTIA_13_NAP-A-III/7, 2017-1.2.1-NKP-2017-00002]; Talentum Foundation of Gedeon Richter Ltd.; Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences [BO/00724/12]; Hungarian Scientific Research Fund [OTKA PD105622] AB - Alzheimer's disease is one of the most common chronic neurodegenerative disorders. Despite several in vivo and clinical studies, the cause of the disease is poorly understood. Currently, amyloid β (Aβ) peptide and its tendency to assemble into soluble oligomers are known as a main pathogenic event leading to the interruption of synapses and brain degeneration. Targeting neurotoxic Aβ oligomers can help recognize the disease at an early stage or it can be a potential therapeutic approach. Unnatural β-peptidic foldamers are successfully used against many different protein targets due to their favorable structural and pharmacokinetic properties compared to small molecule or protein-like drug candidates. We have previously reported a tetravalent foldamer-dendrimer conjugate which can selectively bind Aβ oligomers. Taking advantage of multivalency and foldamers, we synthesized different multivalent foldamer-based conjugates to optimize the geometry of the ligand. Isothermal titration calorimetry (ITC) was used to measure binding affinity to Aβ, thereafter 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based tissue viability assay and impedance-based viability assay on SH-SY5Y cells were applied to monitor Aβ toxicity and protective effects of the compounds. Important factors for high binding affinity were determined and a good correlation was found between influencing the valence and the capability of the conjugates for Aβ binding. LA - English DB - MTMT ER - TY - JOUR AU - Bartus, Éva AU - Hegedüs, Zsófia AU - Wéber, Edit AU - Csipak, Brigitta AU - Szakonyi, Gerda AU - Martinek, Tamás TI - De Novo Modular Development of a Foldameric Protein-Protein Interaction Inhibitor for Separate Hot Spots: A Dynamic Covalent Assembly Approach JF - CHEMISTRYOPEN J2 - CHEMISTRYOPEN VL - 6 PY - 2017 IS - 2 SP - 236 EP - 241 PG - 6 SN - 2191-1363 DO - 10.1002/open.201700012 UR - https://m2.mtmt.hu/api/publication/3213189 ID - 3213189 LA - English DB - MTMT ER - TY - JOUR AU - Olajos, Gábor AU - Bartus, Éva AU - Schuster, Ildikó AU - Lautner, Gergely AU - Gyurcsányi, Ervin Róbert AU - Szögi, Titanilla AU - Fülöp, Lívia AU - Martinek, Tamás TI - Multivalent foldamer-based affinity assay for selective recognition of Aβ oligomers JF - ANALYTICA CHIMICA ACTA J2 - ANAL CHIM ACTA VL - 960 PY - 2017 SP - 131 EP - 137 PG - 7 SN - 0003-2670 DO - 10.1016/j.aca.2017.01.013 UR - https://m2.mtmt.hu/api/publication/3193785 ID - 3193785 N1 - Megjegyzés-26494651 N1 Funding details: TÁMOP-4.2.4.A/2-11/1-2012-0001, ESF, European Social Fund N1 Funding text: This work was supported by the Hungarian Academy of Sciences, Lendület programs (LP-2011-009 and LP2013-63), Gedeon Richter Plc. (TP7-017), the Hungarian Research Foundation (OTKA K112442) and Gedeon Richter's Talentum Foundation (Ph.D. Scholarship to É.B.). This research received financing also from the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program’. This work was supported by the Hungarian Brain Research Program - Grant No. KTIA_13_NAP-A-III/7. Funding Agency and Grant Number: Hungarian Academy of Sciences, Lendulet program [LP-2011-009, LP2013-63]; Gedeon Richter Plc. [TP7-017]; Hungarian Research Foundation [OTKA K112442]; Gedeon Richter's Talentum Foundation; European Union; State of Hungary; European Social Fund 'National Excellence Program' [TAMOP-4.2.4.A/2-11/1-2012-0001]; Hungarian Brain Research Program [KTIA_13_-NAP-A-III/7]\n Funding text: This work was supported by the Hungarian Academy of Sciences, Lendulet programs (LP-2011-009 and LP2013-63), Gedeon Richter Plc. (TP7-017), the Hungarian Research Foundation (OTKA K112442) and Gedeon Richter's Talentum Foundation (Ph.D. Scholarship to E.B.). This research received financing also from the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. This work was supported by the Hungarian Brain Research Program - Grant No. KTIA_13_-NAP-A-III/7.\n Funding Agency and Grant Number: Hungarian Academy of Sciences, Lendulet program [LP-2011-009, LP2013-63]; Gedeon Richter Plc. [TP7-017]; Hungarian Research Foundation [OTKA K112442]; Gedeon Richter's Talentum Foundation; European Union; State of Hungary; European Social Fund 'National Excellence Program' [TAMOP-4.2.4.A/2-11/1-2012-0001]; Hungarian Brain Research Program [KTIA_13_-NAP-A-III/7] Funding text: This work was supported by the Hungarian Academy of Sciences, Lendulet programs (LP-2011-009 and LP2013-63), Gedeon Richter Plc. (TP7-017), the Hungarian Research Foundation (OTKA K112442) and Gedeon Richter's Talentum Foundation (Ph.D. Scholarship to E.B.). This research received financing also from the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. This work was supported by the Hungarian Brain Research Program - Grant No. KTIA_13_-NAP-A-III/7. Institute of Pharmaceutical Analysis, University of Szeged, Somogyi u. 4, Szeged, 6720, Hungary Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary MTA-BME Lendület Chemical Nanosensors Research Group, Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szt. Gellért tér 4, Budapest, 1111, Hungary Cited By :2 Export Date: 24 September 2019 CODEN: ACACA Correspondence Address: Fülöp, L.; Department of Medical Chemistry, University of Szeged, Dóm tér 8, Hungary; email: fulop.livia@med.u-szeged.hu Chemicals/CAS: amyloid beta protein, 109770-29-8; Amyloid beta-Peptides; Protein Aggregates Funding details: Richter Gedeon Talentum Alapítvány Funding details: European Social Fund, ESF, A/2-11/1-2012-0001 Funding details: Magyar Tudományos Akadémia, MTA, LP2013-63, LP-2011-009 Funding details: Gedeon Richter, TP7-017 Funding details: K112442 Funding details: KTIA_13_NAP-A-III/7 Funding text 1: This work was supported by the Hungarian Academy of Sciences, Lend?let programs (LP-2011-009 and LP2013-63), Gedeon Richter Plc. (TP7-017), the Hungarian Research Foundation (OTKA K112442) and Gedeon Richter's Talentum Foundation (Ph.D. Scholarship to ?.B.). This research received financing also from the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of T?MOP-4.2.4.A/2-11/1-2012-0001 ?National Excellence Program?. This work was supported by the Hungarian Brain Research Program - Grant No. KTIA_13_NAP-A-III/7. CAplus AN 2017:198655; MEDLINE PMID: 28193356 (Journal; Article); AB - Abstract Mimicking the molecular recognition functionality of antibodies is a great challenge. Foldamers are attractive candidates because of their relatively small size and designable interaction surface. This paper describes a sandwich type enzyme-linked immunoassay with a tetravalent β-peptide foldamer helix array as capture element and enzyme labeled tracer antibodies. The assay was found to be selective to β-amyloid oligomeric species with surface features transiently present in ongoing aggregation. In optimized conditions, with special emphasis on the foldamer immobilization, a detection limit of 5 pM was achieved with a linear range of 10–500 pM. These results suggest that protein mimetic foldamers can be useful tools in biosensors and affinity assays. LA - English DB - MTMT ER -