TY - JOUR AU - Simon, Péter AU - Lőrinczi, Bálint AU - Hetényi, Anasztázia AU - Szatmári, István TI - Novel Eco-friendly, One-Pot Method for the Synthesis of Kynurenic Acid Ethyl Esters JF - ACS OMEGA J2 - ACS OMEGA VL - 8 PY - 2023 IS - 20 SP - 17966 EP - 17975 PG - 10 SN - 2470-1343 DO - 10.1021/acsomega.3c01170 UR - https://m2.mtmt.hu/api/publication/33811528 ID - 33811528 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 - Yazdani, Morteza AU - Barta, Anita AU - Hetényi, Anasztázia AU - Berkecz, Róbert AU - Spengler, Gabriella AU - Ványolós, Attila AU - Hohmann, Judit TI - Isolation of the Lanostane Triterpenes Pholiols L–S from Pholiota populnea and Evaluation of Their Antiproliferative and Cytotoxic Activities JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 16 PY - 2023 IS - 1 PG - 13 SN - 1424-8247 DO - 10.3390/ph16010104 UR - https://m2.mtmt.hu/api/publication/33552540 ID - 33552540 N1 - Export Date: 25 April 2023 Correspondence Address: Hohmann, J.; Institute of Pharmacognosy, Hungary; email: hohmann.judit@szte.hu LA - English DB - MTMT ER - TY - JOUR AU - Martinek, Tamás AU - Imre, Norbert AU - Hetényi, Anasztázia AU - Szabo, Eniko AU - Bodnar, Brigitta AU - Szkalisity, Abel AU - Grof, Ilona AU - Bocsik, Alexandra AU - Deli, Maria A. AU - Horvath, Peter AU - Czibula, Agnes AU - Monostori, Eva TI - Degradation-free intracellular delivery of nanomolar antibodies through reading the lipid raft sugar code with peptidic tags JF - JOURNAL OF PEPTIDE SCIENCE J2 - J PEPT SCI VL - 28 PY - 2022 PG - 2 SN - 1075-2617 UR - https://m2.mtmt.hu/api/publication/34047583 ID - 34047583 N1 - Supplement: 3 LA - English DB - MTMT ER - TY - JOUR AU - Hetényi, Anasztázia AU - Szabó, Enikő AU - Imre, Norbert AU - Nath Bhaumik, Kaushik AU - Tököli, Attila AU - Füzesi, Tamás AU - Hollandi, Réka AU - Horváth, Péter AU - Czibula, Ágnes AU - Monostori, Éva AU - Deli, Mária Anna AU - Martinek, Tamás TI - α/β-Peptides as Nanomolar Triggers of Lipid Raft-Mediated Endocytosis through GM1 Ganglioside Recognition JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 14 PY - 2022 IS - 3 PG - 11 SN - 1999-4923 DO - 10.3390/pharmaceutics14030580 UR - https://m2.mtmt.hu/api/publication/32733913 ID - 32733913 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of HungaryNational Research, Development & Innovation Office (NRDIO) - Hungary [GINOP-2.2.1-15-2016-00007]; Hungarian Ministry of Innovation and Technology [TUDFO/47138-1/2019-ITM]; Hungarian National Brain Research Program (MTA-SE-NAP B-BIOMAG); Hungarian Academy of Sciences LENDULET-FoldamerHungarian Academy of Sciences; NKFINational Research, Development & Innovation Office (NRDIO) - Hungary [K134754]; Finnish TEKES FiDiPro Fellow Grant [40294/13]; Hungarian Academy of Sciences LENDULET-BiomagHungarian Academy of Sciences; Ministry of Innovation and Technology of Hungary through the National Research, Development and Innovation Fund [TKP2021-EGA-32] Funding text: This research was funded by the National Research, Development and Innovation Office of Hungary, grant number GINOP-2.2.1-15-2016-00007, the Hungarian Ministry of Innovation and Technology, TUDFO/47138-1/2019-ITM, and the Hungarian National Brain Research Program (MTA-SE-NAP B-BIOMAG). T.A.M. acknowledges support from the Hungarian Academy of Sciences LENDULET-Foldamer, and NKFI K134754. P.H. acknowledges support from the Finnish TEKES FiDiPro Fellow Grant 40294/13, and the Hungarian Academy of Sciences LENDULET-Biomag. Support by the Ministry of Innovation and Technology of Hungary through the National Research, Development and Innovation Fund (TKP2021-EGA-32) is acknowledged. AB - Cell delivery of therapeutic macromolecules and nanoparticles is a critical drug development challenge. Translocation through lipid raft-mediated endocytic mechanisms is being sought, as it can avoid rapid lysosomal degradation. Here, we present a set of short alpha/beta-peptide tags with high affinity to the lipid raft-associated ganglioside GM1. These sequences induce effective internalization of the attached immunoglobulin cargo. The structural requirements of the GM1-peptide interaction are presented, and the importance of the membrane components are shown. The results contribute to the development of a receptor-based cell delivery platform. LA - English DB - MTMT ER - TY - JOUR AU - Nath Bhaumik, Kaushik AU - Hetényi, Anasztázia AU - Olajos, Gábor AU - Martins, Ana AU - Spohn, Réka AU - Németh, Lukács AU - Jójárt, Balázs AU - Szili, Petra AU - Dunai, Anett AU - Jangir, Pramod Kumar AU - Daruka, Lejla AU - Földesi, Imre AU - Kata, Diána AU - Pál, Csaba AU - Martinek, Tamás TI - Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization JF - MOLECULAR SYSTEMS DESIGN & ENGINEERING J2 - MOL SYST DES ENG VL - 7 PY - 2022 IS - 1 SP - 21 EP - 33 PG - 13 SN - 2058-9689 DO - 10.1039/D1ME00118C UR - https://m2.mtmt.hu/api/publication/32493048 ID - 32493048 N1 - Funding Agency and Grant Number: European Research CouncilEuropean Research Council (ERC)European Commission [H2020-ERC-2014-CoG 648364, H2020-ERC-2019-PoC 862077]; ELKH Lendulet Programme [LP-2017-10/2020]; National Research, Development and Innovation Office, HungaryNational Research, Development & Innovation Office (NRDIO) - Hungary [KKP 126506]; National Laboratory of Biotechnology Grant [NKFIH-871-3/2020, GINOP-2.3.2-15-2016-00014, GINOP-2.3.2-15-2016-00020]; NKFINational Research, Development & Innovation Office (NRDIO) - Hungary [PD 116222, K134754]; Ministry of Human Capacities, Hungary [20391-3/2018/FEKUSTRAT] Funding text: The study was supported by the following research grants: European Research Council H2020-ERC-2014-CoG 648364-Resistance Evolution (CP); European Research Council H2020-ERC-2019-PoC 862077-Aware (CP), ELKH Lendulet Programme LP-2017-10/2020 (CP); 'Elvonal' Programme KKP 126506 of the National Research, Development and Innovation Office, Hungary (CP), National Laboratory of Biotechnology Grant NKFIH-871-3/2020 (CP), GINOP-2.3.2-15-2016-00014 (EVOMER) (CP, TAM), GINOP-2.3.2-15-2016-00020 (MolMedEx TUMORDNS) (CP), and NKFI PD 116222 (AM), NKFI K134754 (TAM), Ministry of Human Capacities, Hungary grant 20391-3/2018/FEKUSTRAT (TAM). The authors thank Dora Bokor, PharmD, for proofreading the manuscript. AB - The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold of the antimicrobial peptide PGLa, we have developed antimicrobial foldamers with a computer-guided design strategy. The novel PGLa analogues induce sustained membrane hyperpolarization. When co-administered as an adjuvant, the resulting compounds - PGLb1 and PGLb2 - have substantially reduced the level of antibiotic resistance of multi-drug resistant Escherichia coli, Klebsiella pneumoniae and Shigella flexneri clinical isolates. The observed antibiotic potentiation was mediated by hyperpolarization of the bacterial membrane caused by the alteration of cellular ion transport. Specifically, PGLb1 and PGLb2 are selective ionophores that enhance the Goldman-Hodgkin-Katz potential across the bacterial membrane. These findings indicate that manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance. LA - English DB - MTMT ER - TY - JOUR AU - Hetényi, Anasztázia AU - Imre, Norbert AU - Szabó, Enikő AU - Bodnár, Brigitta AU - Szkalisity, Ábel AU - Gróf, Ilona AU - Bocsik, Alexandra AU - Deli, Mária Anna AU - Horváth, Péter AU - Czibula, Ágnes AU - Monostori, Éva AU - Martinek, Tamás TI - Fehérje méretű molekulák humán sejtekbe juttatása lipid-raft mediált endocitózissal JF - BIOKÉMIA: A MAGYAR BIOKÉMIAI EGYESÜLET FOLYÓIRATA J2 - BIOKÉMIA VL - 45 PY - 2021 IS - 4 SP - 67 EP - 83 PG - 17 SN - 0133-8455 UR - https://m2.mtmt.hu/api/publication/32570862 ID - 32570862 N1 - Nincs jelölve levelező szerzőség a közleményen. (BÉ SZTE admin5) LA - Hungarian DB - MTMT ER - TY - PAT AU - Imre, Norbert AU - Martinek, Tamás AU - Hetényi, Anasztázia AU - Bodnár, Brigitta AU - Monostori, Eva AU - Czibula, Agnes AU - Szabo, Eniko AU - Deli, Mária Anna AU - Horvath, Peter TI - Endocytosis routing sequence peptide for cell delivery systems PY - 2020 UR - https://m2.mtmt.hu/api/publication/32024174 ID - 32024174 AB - The present invention relates to cell delivery systems. The present invention specifically relates to new methods of intracellular delivery by endocytosis routing sequence peptides having the sequence of WYKYV or analogs thereof, by caveloar/lipid raft-mediated endocytosis and uses of such peptides. The invention also relates to conjugates comprising said peptides and uses thereof in therapies wherein intracellular delivery of a therapeutically active mol. is required. LA - English DB - MTMT ER - TY - JOUR AU - Petri, László AU - Egyed, Attila AU - Bajusz, Dávid AU - Imre, Timea AU - Hetényi, Anasztázia AU - Martinek, Tamás AU - Ábrányi-Balogh, Péter AU - Keserű, György Miklós TI - An electrophilic warhead library for mapping the reactivity and accessibility of tractable cysteines in protein kinases JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 207 PY - 2020 PG - 9 SN - 0223-5234 DO - 10.1016/j.ejmech.2020.112836 UR - https://m2.mtmt.hu/api/publication/31613727 ID - 31613727 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary (NKFIH) [K116904]; Hungarian Science Foundation OTKA grantOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [PD124598]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences Funding text: This work was supported by the National Research, Development and Innovation Office of Hungary (NKFIH grant number K116904). P. Abranyi-Balogh was supported by the postdoctoral fellowship of the Hungarian Science Foundation OTKA (PD124598) grant. The work of D. Bajusz is supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. The authors are grateful to Balazs Mer}o (RCNS) for the expression of MELK, Zoltan Kele (SZTE) for his contribution to the MS investigation of MELK protein, Gyorgy G. Ferenczy (RCNS) and Greg Makara (ChemPass) for useful discussions on the manuscript. LA - English DB - MTMT ER - TY - JOUR AU - Rachman, Moira AU - Bajusz, Dávid AU - Hetényi, Anasztázia AU - Scarpino, Andrea AU - Merő, Balázs László AU - Egyed, Attila AU - Buday, László AU - Barril, Xavier AU - Keserű, György Miklós TI - Discovery of a novel kinase hinge binder fragment by dynamic undocking JF - RSC MEDICINAL CHEMISTRY J2 - RSC MED CHEM VL - 11 PY - 2020 IS - 5 SP - 552 EP - 558 PG - 7 SN - 2632-8682 DO - 10.1039/C9MD00519F UR - https://m2.mtmt.hu/api/publication/31205779 ID - 31205779 N1 - Funding Agency and Grant Number: MSCA ITN FRAGNET [6758993]; National Research, Development and Innovation Office of Hungary [OTKA K116904]; MCIU/AEI/FEDER, UE [SAF2015-68749-R, RTI2018-096429-B-I00]; Catalan government [2014 SGR 1189]; National Research, Development and Innovation Fund of Hungary [HunProEx 2018-1.2.1-NKP-201800005] Funding text: The authors thank Kitti Koprivanacz and Tamas Szimler for their help in protein expression and purification. This study was supported by the MSCA ITN FRAGNET (project 6758993) grant to M. R., A. S., X. B. and G. M. K., by the National Research, Development and Innovation Office of Hungary (OTKA K116904), the MCIU/AEI/FEDER, UE (SAF2015-68749-R and RTI2018-096429-B-I00), the Catalan government (2014 SGR 1189), and the National Research, Development and Innovation Fund of Hungary (HunProEx 2018-1.2.1-NKP-201800005). LA - English DB - MTMT ER -