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 - Manteghi, Reihaneh AU - Pallagi, Edina AU - Olajos, Gábor AU - Pannonhalminé Csóka, Ildikó TI - Pegylation and formulation strategy of Anti-Microbial Peptide (AMP) according to the quality by design approach JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 144 PY - 2020 PG - 9 SN - 0928-0987 DO - 10.1016/j.ejps.2019.105197 UR - https://m2.mtmt.hu/api/publication/31042655 ID - 31042655 N1 - DOI: 10.1016/j.ejps.2019.105197 LA - English DB - MTMT ER - TY - THES AU - Olajos, Gábor TI - Beta-amino acid substitutions in beta-sandwich model proteins PB - Szegedi Tudományegyetem (SZTE) PY - 2019 SP - 54 DO - 10.14232/phd.10055 UR - https://m2.mtmt.hu/api/publication/30808759 ID - 30808759 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 - Olajos, Gábor AU - Hetényi, Anasztázia AU - Wéber, Edit AU - Szögi, Titanilla AU - Fülöp, Lívia AU - Martinek, Tamás TI - Peripheral cyclic β-amino acids balance the stability and edge-protection of β-sandwiches JF - ORGANIC & BIOMOLECULAR CHEMISTRY J2 - ORG BIOMOL CHEM VL - 16 PY - 2018 IS - 30 SP - 5492 EP - 5499 PG - 8 SN - 1477-0520 DO - 10.1039/c8ob01322e UR - https://m2.mtmt.hu/api/publication/3399101 ID - 3399101 N1 - Funding text: This work was supported by the Hungarian Academy of Sciences, Lendulet program (LP-2011-009) and GINOP-2.3.3-15-2016-00010. E. W. thanks the Postdoctoral Fellowship Program 2014 of the Hungarian Academy of Sciences. AB - Engineering water-soluble stand-alone beta-sandwich mimetics is a current challenge because of the difficulties associated with tailoring long-range interactions. In this work, single cis-(1R,2S)-2-aminocyclohexanecarboxylic acid mutations were introduced into the edge strands of the eight-stranded beta-sandwich mimetic structures from the betabellin family. Temperature-dependent NMR and CD measurements, together with thermodynamic analyses, demonstrated that the modified peripheral strands exhibited an irregular and partially disordered structure but were able to exert sufficient shielding on the hydrophobic core to retain the predominantly beta-sandwich structure. Although the frustrated interactions decreased the free energy of unfolding, the temperature of the maximum stabilities increased to or remained at physiologically relevant temperatures. We found that the irregular peripheral strands were able to prevent edge-to-edge association and fibril formation in the aggregation-prone model. These findings establish a beta-sandwich stabilization and aggregation inhibition approach, which does not interfere with the pillars of the peptide bond or change the net charge of the peptide. LA - English DB - MTMT ER - TY - JOUR AU - Lázár, Viktória AU - Martins, Ana AU - Spohn, Réka AU - Daruka, Lejla AU - Grézal, Gábor AU - Fekete, Gergely AU - Számel, Mónika AU - Jangir, Pramod Kumar AU - Kintses, Bálint AU - Csörgő, Bálint AU - Nyerges, Ákos AU - Györkei, Ádám AU - Kincses, András AU - Dér, András AU - Walter, Fruzsina AU - Deli, Mária Anna AU - Zsoldiné Urbán, Edit AU - Hegedüs, Zsófia AU - Olajos, Gábor AU - Méhi, Orsolya Katinka AU - Bálint, Balázs AU - Nagy, István AU - Martinek, Tamás AU - Papp, Balázs AU - Pál, Csaba TI - Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides JF - NATURE MICROBIOLOGY J2 - NAT MICROBIOL VL - 3 PY - 2018 IS - 6 SP - 718 EP - 731 PG - 14 SN - 2058-5276 DO - 10.1038/s41564-018-0164-0 UR - https://m2.mtmt.hu/api/publication/3378998 ID - 3378998 N1 - Megosztott első szerzőség. These authors contributed equally to this work: Viktória Lázár and Ana Martins. AB - Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections. 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 - TY - JOUR AU - Olajos, Gábor AU - Hetényi, Anasztázia AU - Wéber, Edit AU - Németh, Lukács AU - Szakonyi, Zsolt AU - Fülöp, Ferenc AU - Martinek, Tamás TI - Induced Folding of Protein-Sized Foldameric β-Sandwich Models with Core β-Amino Acid Residues JF - CHEMISTRY-A EUROPEAN JOURNAL J2 - CHEM-EUR J VL - 21 PY - 2015 IS - 16 SP - 6173 EP - 6180 PG - 8 SN - 0947-6539 DO - 10.1002/chem.201405581 UR - https://m2.mtmt.hu/api/publication/2868602 ID - 2868602 N1 - Funding Agency and Grant Number: Hungarian Academy of Sciences (Lendulet program) [LP-2011-009]; Gedeon Richter Plc. [TP7-017]; Hungarian Research Foundation [OTKA K112442]\n Funding text: This work was supported by the Hungarian Academy of Sciences (Lendulet program LP-2011-009), Gedeon Richter Plc. (TP7-017), and the Hungarian Research Foundation (OTKA K112442). Computations were carried out at the HPC Center of the University of Szeged (TAMOP-4.2.2.C-11/1/KONV-2012-0010).\n Funding Agency and Grant Number: Hungarian Academy of Sciences (Lendulet program) [LP-2011-009]; Gedeon Richter Plc. [TP7-017]; Hungarian Research FoundationOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K112442] Funding text: This work was supported by the Hungarian Academy of Sciences (Lendulet program LP-2011-009), Gedeon Richter Plc. (TP7-017), and the Hungarian Research Foundation (OTKA K112442). Computations were carried out at the HPC Center of the University of Szeged (TAMOP-4.2.2.C-11/1/KONV-2012-0010). CAplus AN 2015:484036; MEDLINE PMID: 25677195 (Journal; Article; Research Support, Non-U.S. Gov't); AB - The mimicry of protein-sized β-sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin-14 β-sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β-Residues with diverse structural properties were utilized: Homologous β3-amino acids, (1R,2S)-2-aminocyclopentanecarboxylic acid (ACPC), (1R,2S)-2-aminocyclohexanecarboxylic acid (ACHC), (1R,2S)-2-aminocyclohex-3-enecarboxylic acid (ACEC), and (1S,2S,3R,5S)-2-amino-6,6-dimethylbicyclo[3.1.1]heptane-3-carboxylic acid (ABHC). Six α/β-peptidic chains were constructed in both monomeric and disulfide-linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β-sheet formation in the 64-residue foldameric systems. Core replacement with (1R,2S)-ACHC was found to be unique among the β-amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen-bonding network and to fit sterically into the hydrophobic interior of the β-sandwich. The novel β-sandwich model containing 25% unnatural building blocks afforded protein-like thermal denaturation behavior. Dissolving sandwiches: A water-soluble β-sandwich has been constructed by using cyclic β-amino acids in the hydrophobic core (see figure). The structural stability is highly dependent on the side-chain, and the destructuring effects of the β-residues could be minimized by using (1R,2S)-2-aminocyclohexanecarboxylic acid. The β-sandwich displays protein-like thermal denaturation behavior. LA - English DB - MTMT ER - TY - JOUR AU - Mándity, István AU - Wéber, Edit AU - Martinek, Tamás AU - Olajos, Gábor AU - Tóth, Gábor AU - Vass, Elemér AU - Fülöp, Ferenc TI - Design of Peptidic Foldamer Helices: A Stereochemical Patterning Approach JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION J2 - ANGEW CHEM INT EDIT VL - 48 PY - 2009 IS - 12 SP - 2171 EP - 2175 PG - 5 SN - 1433-7851 DO - 10.1002/anie.200805095 UR - https://m2.mtmt.hu/api/publication/1232853 ID - 1232853 N1 - Institutes of Pharmaceutical Chemistry and Medical Chemistry, Universitiy of Szeged, Etvs u. 6, 6720 Szeged, Hungary Department of Organic Chemistry, Etvs Loránd University, Pázmány P. s. 1A, 1117 Budapest, Hungary Cited By :101 Export Date: 5 April 2024 CODEN: ACIEA Correspondence Address: Mándity, I. M.; Institutes of Pharmaceutical Chemistry and Medical Chemistry, Etvs u. 6, 6720 Szeged, Hungary LA - English DB - MTMT ER -