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 - Kupihár, Zoltán AU - Ferenc, Györgyi AU - Petrovicz, Vencel László AU - Fáy, Viktória R. AU - Kovács, Lajos AU - Martinek, Tamás AU - Hegedüs, Zsófia TI - Improved Metal-Free Approach for the Synthesis of Protected Thiol Containing Thymidine Nucleoside Phosphoramidite and Its Application for the Synthesis of Ligatable Oligonucleotide Conjugates JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 1 PG - 16 SN - 1999-4923 DO - 10.3390/pharmaceutics15010248 UR - https://m2.mtmt.hu/api/publication/33597958 ID - 33597958 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFIH PD 135324, K 128801, K 134754]; Ministry of Innovation and Technology of Hungary through the National Research, Development and Innovation Fund [TKP2021-EGA-32] Funding text: This work received funding from the National Research, Development and Innovation Office of Hungary-NKFIH PD 135324 (Z.H.), K 128801 (L.K.) and K 134754 (T.A.M.). Support by the Ministry of Innovation and Technology of Hungary through the National Research, Development and Innovation Fund (TKP2021-EGA-32) is acknowledged. AB - Oligonucleotide conjugates are versatile scaffolds that can be applied in DNA-based screening platforms and ligand display or as therapeutics. Several different chemical approaches are available for functionalizing oligonucleotides, which are often carried out on the 5′ or 3′ end. Modifying oligonucleotides in the middle of the sequence opens the possibility to ligate the conjugates and create DNA strands bearing multiple different ligands. Our goal was to establish a complete workflow that can be applied for such purposes from monomer synthesis to templated ligation. To achieve this, a monomer is required with an orthogonal functional group that can be incorporated internally into the oligonucleotide sequence. This is followed by conjugation with different molecules and ligation with the help of a complementary template. Here, we show the synthesis and the application of a thiol-modified thymidine nucleoside phosphoramidite to prepare ligatable oligonucleotide conjugates. The conjugations were performed both in solution and on solid phase, resulting in conjugates that can be assembled into multivalent oligonucleotides decorated with tissue-targeting peptides using templated ligation. 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 - 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 - 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 - Makra, Zsófia AU - Madácsi, Ramóna AU - Martinek, Tamás AU - Bényei, Attila Csaba AU - Puskás, László AU - Gyuris, Márió AU - Kanizsai, Iván TI - Phosphine(III)‐Triggered One‐Pot Domino Sequences towards 5,6‐Dihydropyridine‐2‐(1 H )‐One and Pyridine‐2(1 H )‐One Scaffolds JF - ADVANCED SYNTHESIS & CATALYSIS J2 - ADV SYNTH CATAL VL - 364 PY - 2022 IS - 6 SP - 1134 EP - 1143 PG - 10 SN - 1615-4150 DO - 10.1002/adsc.202101370 UR - https://m2.mtmt.hu/api/publication/32743393 ID - 32743393 N1 - AVIDIN Ltd., Alsó kikötő sor 11/D, Szeged, H-6726, Hungary University of Szeged, Department of Medical Chemistry, Dóm tér 8, Szeged, H-6720, Hungary University of Debrecen, Department of Physical Chemistry, Laboratory for X-ray Diffraction, Egyetem tér 1, Debrecen, H-4032, Hungary Export Date: 13 June 2022 CODEN: ASCAF Correspondence Address: Gyuris, M.; AVIDIN Ltd., Hungary; email: m.gyuris@avidinbiotech.com Correspondence Address: Kanizsai, I.; AVIDIN Ltd., Hungary; email: i.kanizsai@avidinbiotech.com 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 - Németh, Lukács AU - Martinek, Tamás AU - Jójárt, Balázs TI - Tilted State Population of Antimicrobial Peptide PGLa Is Coupled to the Transmembrane Potential JF - JOURNAL OF CHEMICAL INFORMATION AND MODELING J2 - J CHEM INF MODEL VL - 62 PY - 2022 IS - 20 SP - 4963 EP - 4969 PG - 7 SN - 1549-9596 DO - 10.1021/acs.jcim.2c00667 UR - https://m2.mtmt.hu/api/publication/33225790 ID - 33225790 N1 - Export Date: 5 September 2023 CODEN: JCISD Correspondence Address: Jójárt, B.; Institute of Food Engineering, Mars tér 7, Hungary; email: jojartb@mk.u-szeged.hu Correspondence Address: Martinek, T.A.; Department of Medical Chemistry, Dóm tér 8, Hungary; email: martinek.tamas@med.u-szeged.hu Chemicals/CAS: water, 7732-18-5; Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Peptides; Lipid Bilayers; Water Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, K134754, TKP2021-EGA-32 Funding text 1: This work is supported by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund TKP2021-EGA-32 and K134754 is acknowledged. 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 - 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 - 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 - 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 - Imre, Norbert AU - Hetényi, Anasztázia 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 - Routing Nanomolar Protein Cargoes to Lipid Raft‐Mediated/Caveolar Endocytosis through a Ganglioside GM1‐Specific Recognition Tag JF - ADVANCED SCIENCE J2 - ADV SCI VL - 7 PY - 2020 IS - 4 PG - 10 SN - 2198-3844 DO - 10.1002/advs.201902621 UR - https://m2.mtmt.hu/api/publication/31126947 ID - 31126947 N1 - 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 Hungarian National Brain Research Program (MTA-SE-NAP B-BIOMAG). T.A.M. acknowledges support from the Hungarian Academy of Sciences LENDULET-Foldamer. P.H. acknowledges support from the Finnish TEKES FiDiPro Fellow Grant 40294/13, the Hungarian Academy of Sciences LENDULET-Biomag. 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 - 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 - JOUR AU - Turalic, Amila AU - Dedibegovic, Jasmina AU - Hegedüs, Zsófia AU - Martinek, Tamás TI - DPP-4 Cleaves alpha/beta-Peptide Bonds: Substrate Specificity and Half-Lives JF - CHEMBIOCHEM J2 - CHEMBIOCHEM VL - 21 PY - 2020 IS - 14 SP - 2060 EP - 2066 PG - 7 SN - 1439-4227 DO - 10.1002/cbic.202000050 UR - https://m2.mtmt.hu/api/publication/31371344 ID - 31371344 N1 - Department of Pharmaceutical Analysis, University of Sarajevo, Faculty of Pharmacy, Zmaja od Bosne 8, Sarajevo, 71 000, Bosnia and Herzegovina Department of Medical Chemistry, University of Szeged, Faculty of Medicine, 8 Dóm tér, Szeged, 6720, Hungary MTA-SZTE Biomimetic Systems Research Group, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary Cited By :2 Export Date: 8 September 2023 CODEN: CBCHF Correspondence Address: Hegedüs, Z.; Department of Medical Chemistry, 8 Dóm tér, Hungary; email: hegedus.zsofia@med.u-szeged.hu Correspondence Address: Martinek, T.A.; Department of Medical Chemistry, 8 Dóm tér, Hungary; email: martinek.tamas@med.u-szeged.hu Correspondence Address: Martinek, T.A.; MTA-SZTE Biomimetic Systems Research Group, Dóm tér 8, Hungary; email: martinek.tamas@med.u-szeged.hu AB - The incorporation of beta-amino acids into a peptide sequence has gained particular attention as beta- and alpha/beta-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specificity but at a much slower rate compared to alpha-peptide bonds. In this study, a series of analogs of dipeptidyl peptidase-4 (DPP-4) substrate inhibitors were synthesized in order to investigate whether beta-amino acid homologation at the scissile bond could be a valid approach to improving peptide stability towards DPP-4 degradation. DPP-4 cleaved the alpha/beta-peptide bond after the N-terminal penultimate Pro with a broad specificity and retained full activity regardless of the beta(3)-amino acid side chain and peptide length. Significantly improved half-lives were observed for beta(3)Ile-containing peptides. Replacing the penultimate Pro with a conformationally constrained Pro mimetic led to proteolytic resistance. DPP-4 cleavage of alpha/beta-peptide bonds with a broad promiscuity represents a new insight into the stability of peptide analogs containing beta-amino acids as such analogs were thought to be stable towards enzymatic degradation. 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 - JOUR AU - Bocsik, Alexandra AU - Gróf, Ilona AU - Kiss, Lóránd AU - Ötvös, Ferenc AU - Zsíros, Ottó AU - Daruka, Lejla AU - Fülöp, Lívia AU - Vastag, Monika AU - Kittel, Ágnes AU - Imre, Norbert AU - Martinek, Tamás AU - Pál, Csaba AU - Révész, Piroska AU - Deli, Mária Anna TI - Dual Action of the PN159/KLAL/MAP Peptide. Increase of Drug Penetration across Caco-2 Intestinal Barrier Model by Modulation of Tight Junctions and Plasma Membrane Permeability. TS - Increase of Drug Penetration across Caco-2 Intestinal Barrier Model by Modulation of Tight Junctions and Plasma Membrane Permeability. JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 11 PY - 2019 IS - 2 PG - 21 SN - 1999-4923 DO - 10.3390/pharmaceutics11020073 UR - https://m2.mtmt.hu/api/publication/30434125 ID - 30434125 AB - The absorption of drugs is limited by the epithelial barriers of the gastrointestinal tract. One of the strategies to improve drug delivery is the modulation of barrier function by the targeted opening of epithelial tight junctions. In our previous study the 18-mer amphiphilic PN159 peptide was found to be an effective tight junction modulator on intestinal epithelial and blood⁻brain barrier models. PN159, also known as KLAL or MAP, was described to interact with biological membranes as a cell-penetrating peptide. In the present work we demonstrated that the PN159 peptide as a penetration enhancer has a dual action on intestinal epithelial cells. The peptide safely and reversibly enhanced the permeability of Caco-2 monolayers by opening the intercellular junctions. The penetration of dextran molecules with different size and four efflux pump substrate drugs was increased several folds. We identified claudin-4 and -7 junctional proteins by docking studies as potential binding partners and targets of PN159 in the opening of the paracellular pathway. In addition to the tight junction modulator action, the peptide showed cell membrane permeabilizing and antimicrobial effects. This dual action is not general for cell-penetrating peptides (CPPs), since the other three CPPs tested did not show barrier opening effects. LA - English DB - MTMT ER - TY - JOUR AU - Fenteany, Gabriel AU - Gaur, Paras AU - Hegedűs, Lili AU - Dudás, Kata AU - Kiss, Ernő AU - Wéber, Edit AU - Hackler, László AU - Martinek, Tamás AU - Puskás, László AU - Haracska, Lajos TI - Multilevel structure–activity profiling reveals multiple green tea compound families that each modulate ubiquitin-activating enzyme and ubiquitination by a distinct mechanism JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 9 PY - 2019 IS - 1 PG - 16 SN - 2045-2322 DO - 10.1038/s41598-019-48888-6 UR - https://m2.mtmt.hu/api/publication/30791081 ID - 30791081 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [GINOP-2.3.2-15-2016-00020, GINOP-2.3.2-15-2016-00026]; European Union [739593] Funding text: We wish to thank Katalin Kovacs, Gaurav Sharma, Lajos Pinter, and Monika Morocz for technical assistance. This work was supported by the National Research, Development and Innovation Office (GINOP-2.3.2-15-2016-00020 and GINOP-2.3.2-15-2016-00026). This project has also received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 739593. HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Institute of Genetics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, 6726, Hungary Department of Medical Chemistry, University of Szeged, Szeged, 6720, Hungary AstridBio Technologies Ltd., Szeged, 6726, Hungary Laboratory of Functional Genomics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, 6726, Hungary Avicor Ltd., Szeged, 6726, Hungary Cited By :2 Export Date: 11 May 2021 Correspondence Address: Fenteany, G.; HCEMM-BRC Mutagenesis and Carcinogenesis Research Group, Hungary; email: fenteany.gabriel@brc.mta.hu Funding Agency and Grant Number: National Research, Development and Innovation OfficeNational Research, Development & Innovation Office (NRDIO) - Hungary [GINOP-2.3.2-15-2016-00020, GINOP-2.3.2-15-2016-00026]; European UnionEuropean Commission [739593] Funding text: We wish to thank Katalin Kovacs, Gaurav Sharma, Lajos Pinter, and Monika Morocz for technical assistance. This work was supported by the National Research, Development and Innovation Office (GINOP-2.3.2-15-2016-00020 and GINOP-2.3.2-15-2016-00026). This project has also received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 739593. LA - English DB - MTMT ER - TY - GEN AU - Imre, Norbert AU - Hetényi, Anasztázia AU - Szabó, Enikő AU - Bodnár, Brigitta AU - Szkalisity, Ábel AU - Gróf, Ilona AU - Bocsik, Alexandra AU - Deli, A. Mária AU - Horváth, Péter AU - Czibula, Ágnes AU - Monostori, Éva AU - Martinek, Tamás TI - IgG bejuttatása specifikus GM1 gangliozid felismerő szekvenciával PY - 2019 UR - https://m2.mtmt.hu/api/publication/31624665 ID - 31624665 LA - Hungarian DB - MTMT ER -