@article{MTMT:32493048, title = {Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization}, url = {https://m2.mtmt.hu/api/publication/32493048}, author = {Nath Bhaumik, Kaushik and Hetényi, Anasztázia and Olajos, Gábor and Martins, Ana and Spohn, Réka and Németh, Lukács and Jójárt, Balázs and Szili, Petra and Dunai, Anett and Jangir, Pramod Kumar and Daruka, Lejla and Földesi, Imre and Kata, Diána and Pál, Csaba and Martinek, Tamás}, doi = {10.1039/D1ME00118C}, journal-iso = {MOL SYST DES ENG}, journal = {MOLECULAR SYSTEMS DESIGN & ENGINEERING}, volume = {7}, unique-id = {32493048}, issn = {2058-9689}, abstract = {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.}, year = {2022}, eissn = {2058-9689}, pages = {21-33}, orcid-numbers = {Hetényi, Anasztázia/0000-0001-8080-6992; Jangir, Pramod Kumar/0000-0001-8330-0655; Földesi, Imre/0000-0002-3329-8136; Kata, Diána/0000-0002-4432-9380; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:31042655, title = {Pegylation and formulation strategy of Anti-Microbial Peptide (AMP) according to the quality by design approach}, url = {https://m2.mtmt.hu/api/publication/31042655}, author = {Manteghi, Reihaneh and Pallagi, Edina and Olajos, Gábor and Pannonhalminé Csóka, Ildikó}, doi = {10.1016/j.ejps.2019.105197}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {144}, unique-id = {31042655}, issn = {0928-0987}, year = {2020}, eissn = {1879-0720}, orcid-numbers = {Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @mastersthesis{MTMT:30808759, title = {Beta-amino acid substitutions in beta-sandwich model proteins}, url = {https://m2.mtmt.hu/api/publication/30808759}, author = {Olajos, Gábor}, doi = {10.14232/phd.10055}, publisher = {SZTE}, unique-id = {30808759}, year = {2019}, orcid-numbers = {Olajos, Gábor/0000-0002-2479-4891} } @article{MTMT:30310687, title = {Structural optimization of foldamer-dendrimer conjugates as multivalent agents against the toxic effects of amyloid beta oligomers}, url = {https://m2.mtmt.hu/api/publication/30310687}, author = {Bartus, Éva and Olajos, Gábor and Schuster, Ildikó and Bozsó, Zsolt and Deli, Mária Anna and Veszelka, Szilvia and Walter, Fruzsina and Datki, Zsolt László and Szakonyi, Zsolt and Martinek, Tamás and Fülöp, Lívia}, doi = {10.3390/molecules23102523}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {23}, unique-id = {30310687}, issn = {1420-3049}, abstract = {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.}, keywords = {MOLECULAR RECOGNITION; protein aggregation; foldamer; Multivalency; amyloid β}, year = {2018}, eissn = {1420-3049}, orcid-numbers = {Bartus, Éva/0000-0001-9976-6978; Olajos, Gábor/0000-0002-2479-4891; Schuster, Ildikó/0000-0001-9997-5729; Bozsó, Zsolt/0000-0002-5713-3096; Deli, Mária Anna/0000-0001-6084-6524; Walter, Fruzsina/0000-0001-8145-2823; Datki, Zsolt László/0000-0002-2537-4741; Szakonyi, Zsolt/0000-0003-2432-8409; Martinek, Tamás/0000-0003-3168-8066; Fülöp, Lívia/0000-0002-8010-0129} } @article{MTMT:3399101, title = {Peripheral cyclic β-amino acids balance the stability and edge-protection of β-sandwiches}, url = {https://m2.mtmt.hu/api/publication/3399101}, author = {Olajos, Gábor and Hetényi, Anasztázia and Wéber, Edit and Szögi, Titanilla and Fülöp, Lívia and Martinek, Tamás}, doi = {10.1039/c8ob01322e}, journal-iso = {ORG BIOMOL CHEM}, journal = {ORGANIC & BIOMOLECULAR CHEMISTRY}, volume = {16}, unique-id = {3399101}, issn = {1477-0520}, abstract = {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.}, keywords = {INHIBITORS; SECONDARY STRUCTURE; DE-NOVO DESIGN; HEAT-CAPACITY; ALPHA/BETA-PEPTIDES; protein–protein interactions; SHEET PROTEIN; FOLDING THERMODYNAMICS; GAMMA-PEPTIDES}, year = {2018}, eissn = {1477-0539}, pages = {5492-5499}, orcid-numbers = {Olajos, Gábor/0000-0002-2479-4891; Hetényi, Anasztázia/0000-0001-8080-6992; Wéber, Edit/0000-0002-5904-0619; Szögi, Titanilla/0000-0002-9854-7340; Fülöp, Lívia/0000-0002-8010-0129; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:3378998, title = {Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides}, url = {https://m2.mtmt.hu/api/publication/3378998}, author = {Lázár, Viktória and Martins, Ana and Spohn, Réka and Daruka, Lejla and Grézal, Gábor and Fekete, Gergely and Számel, Mónika and Jangir, Pramod Kumar and Kintses, Bálint and Csörgő, Bálint and Nyerges, Ákos and Györkei, Ádám and Kincses, András and Dér, András and Walter, Fruzsina and Deli, Mária Anna and Zsoldiné Urbán, Edit and Hegedüs, Zsófia and Olajos, Gábor and Méhi, Orsolya Katinka and Bálint, Balázs and Nagy, István and Martinek, Tamás and Papp, Balázs and Pál, Csaba}, doi = {10.1038/s41564-018-0164-0}, journal-iso = {NAT MICROBIOL}, journal = {NATURE MICROBIOLOGY}, volume = {3}, unique-id = {3378998}, issn = {2058-5276}, abstract = {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.}, year = {2018}, eissn = {2058-5276}, pages = {718-731}, orcid-numbers = {Grézal, Gábor/0000-0003-1685-4791; Jangir, Pramod Kumar/0000-0001-8330-0655; Csörgő, Bálint/0000-0003-0397-6845; Nyerges, Ákos/0000-0002-1581-490X; Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524; Zsoldiné Urbán, Edit/0000-0002-9602-7552; Hegedüs, Zsófia/0000-0002-5546-8167; Olajos, Gábor/0000-0002-2479-4891; Méhi, Orsolya Katinka/0009-0004-7918-913X; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:3193785, title = {Multivalent foldamer-based affinity assay for selective recognition of Aβ oligomers}, url = {https://m2.mtmt.hu/api/publication/3193785}, author = {Olajos, Gábor and Bartus, Éva and Schuster, Ildikó and Lautner, Gergely and Gyurcsányi, Ervin Róbert and Szögi, Titanilla and Fülöp, Lívia and Martinek, Tamás}, doi = {10.1016/j.aca.2017.01.013}, journal-iso = {ANAL CHIM ACTA}, journal = {ANALYTICA CHIMICA ACTA}, volume = {960}, unique-id = {3193785}, issn = {0003-2670}, abstract = {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.}, keywords = {FOLDAMERS; MOLECULAR RECOGNITION; Antibody mimetics; Bioaffinity assay; β-Amyloid oligomers}, year = {2017}, eissn = {1873-4324}, pages = {131-137}, orcid-numbers = {Olajos, Gábor/0000-0002-2479-4891; Bartus, Éva/0000-0001-9976-6978; Schuster, Ildikó/0000-0001-9997-5729; Gyurcsányi, Ervin Róbert/0000-0002-9929-7865; Szögi, Titanilla/0000-0002-9854-7340; Fülöp, Lívia/0000-0002-8010-0129; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:2868602, title = {Induced Folding of Protein-Sized Foldameric β-Sandwich Models with Core β-Amino Acid Residues}, url = {https://m2.mtmt.hu/api/publication/2868602}, author = {Olajos, Gábor and Hetényi, Anasztázia and Wéber, Edit and Németh, Lukács and Szakonyi, Zsolt and Fülöp, Ferenc and Martinek, Tamás}, doi = {10.1002/chem.201405581}, journal-iso = {CHEM-EUR J}, journal = {CHEMISTRY-A EUROPEAN JOURNAL}, volume = {21}, unique-id = {2868602}, issn = {0947-6539}, abstract = {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.}, keywords = {PROTEINS; STABILITY; Protein Folding; Chemical bonds; amino acids; PEPTIDOMIMETICS; DICHROISM; molecular dynamics; chemical analysis; DYES; Hydrophobicity; Hydrogen bonds; molecular dynamics simulations; CHAINS; circular dichroism spectroscopy; Structural stabilities; Protein Engineering; Thermal denaturations; Hydrogen bonding network; NMR chemical shifts; PROTEIN STRUCTURES}, year = {2015}, eissn = {1521-3765}, pages = {6173-6180}, orcid-numbers = {Hetényi, Anasztázia/0000-0001-8080-6992; Wéber, Edit/0000-0002-5904-0619; Szakonyi, Zsolt/0000-0003-2432-8409; Fülöp, Ferenc/0000-0003-1066-5287; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:1232853, title = {Design of Peptidic Foldamer Helices: A Stereochemical Patterning Approach}, url = {https://m2.mtmt.hu/api/publication/1232853}, author = {Mándity, István and Wéber, Edit and Martinek, Tamás and Olajos, Gábor and Tóth, Gábor and Vass, Elemér and Fülöp, Ferenc}, doi = {10.1002/anie.200805095}, journal-iso = {ANGEW CHEM INT EDIT}, journal = {ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, volume = {48}, unique-id = {1232853}, issn = {1433-7851}, keywords = {SEQUENCES; SECONDARY STRUCTURE; CONFORMATIONS; DE-NOVO DESIGN; PROTEINOGENIC SIDE-CHAINS; FOLDAMERS; OLIGOMERS; amino acids; NMR spectroscopy; ALPHA/BETA-PEPTIDES; helical structures; BETA-AMINO-ACID; BETA(3)-PEPTIDES}, year = {2009}, eissn = {1521-3773}, pages = {2171-2175}, orcid-numbers = {Mándity, István/0000-0003-2865-6143; Wéber, Edit/0000-0002-5904-0619; Martinek, Tamás/0000-0003-3168-8066; Olajos, Gábor/0000-0002-2479-4891; Tóth, Gábor/0000-0002-3604-4385; Vass, Elemér/0000-0001-8898-3846; Fülöp, Ferenc/0000-0003-1066-5287} }