@article{MTMT:34145694,
	title = {Conjugation with Tris Decreases the Risk of Ketoprofen-Induced Mucosal Damage and Reduces Inflammation-Associated Methane Production in a Rat Model of Colitis},
	url = {https://m2.mtmt.hu/api/publication/34145694},
	author = {Ugocsai, Melinda and Bársony, Anett and Varga, Réka A. and Gajda, Ámos and Vida, Noémi and Lajkó, Norbert and Rónaszéki, Benedek and Tóth, Gábor and Boros, Mihály and Érces, Dániel and Varga, Gabriella},
	doi = {10.3390/pharmaceutics15092329},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {15},
	unique-id = {34145694},
	issn = {1999-4923},
	abstract = {We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments.},
	keywords = {Inflammation; MICROCIRCULATION; MUCOSA; TNBS colitis; Non-steroid anti-inflammatory drugs; methane generation; rat},
	year = {2023},
	eissn = {1999-4923},
	orcid-numbers = {Tóth, Gábor/0000-0002-3604-4385; Boros, Mihály/0000-0003-1410-1999; Érces, Dániel/0000-0002-4283-2441; Varga, Gabriella/0000-0003-1888-8629}
}

@article{MTMT:34127552,
	title = {Interaction of biomolecules with anatase, rutile and amorphous TiO2 surfaces: A molecular dynamics study},
	url = {https://m2.mtmt.hu/api/publication/34127552},
	author = {Tarjányi, Tamás and Bogár, Ferenc and Minárovits, János and Gajdács, Márió and Tóth, Zsolt},
	doi = {10.1371/journal.pone.0289467},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {18},
	unique-id = {34127552},
	issn = {1932-6203},
	abstract = {The adhesion of biomolecules to dental and orthopedic implants is a fundamental step in the process of osseointegration. Short peptide motifs, such as RGD or KRSR, carried by extracellular matrix proteins or coated onto implant surfaces, accelerate cell adhesion and tissue formation. For this reason, understanding the binding mechanisms of adhesive peptides to oxidized surfaces of titanium implants is of paramount importance. We performed molecular dynamics simulations to compare the adhesion properties of 6 peptides, including the tripeptide RGD, its variants KGD and LGD, as well as the tetrapeptide KRSR, its variant LRSR and its truncated version RSR, on anatase, rutile, and amorphous titanium dioxide (TiO 2 ) surfaces. The migration of these molecules from the water phase to the surface was simulated in an aqueous environment. Based on these simulations, we calculated the residence time of each peptide bound to the three different TiO 2 structures. It was found that the presence of an N-terminal lysine or arginine amino acid residue resulted in more efficient surface binding. A pulling simulation was performed to detach the adhered molecules. The maximum pulling force and the binding energy were determined from the results of these simulations. The tri- and tetrapeptides had slightly greater adhesion affinity to the amorphous and anatase structure than to rutile in general, however specific surface and peptide binding characters could be detected. The binding energies obtained from our simulations allowed us to rank the adhesion strengths of the studied peptides.},
	year = {2023},
	eissn = {1932-6203},
	orcid-numbers = {Tarjányi, Tamás/0000-0002-9481-5977; Bogár, Ferenc/0000-0002-0611-1452; Gajdács, Márió/0000-0003-1270-0365}
}

@article{MTMT:34117220,
	title = {Protective Effects of Pituitary Adenylate-Cyclase-Activating Polypeptide on Retinal Vasculature and Molecular Responses in a Rat Model of Moderate Glaucoma},
	url = {https://m2.mtmt.hu/api/publication/34117220},
	author = {Patkó, Evelin Viktória and Szabó, Edina and Váczy, Alexandra and Molitor, Dorottya and Tari, Eniko and Li, Lina and Csutak, Adrienne and Tóth, Gábor and Reglődi, Dóra and Atlasz, Tamás},
	doi = {10.3390/ijms241713256},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34117220},
	issn = {1661-6596},
	abstract = {Despite the high probability of glaucoma-related blindness, its cause is not fully understood and there is no efficient therapeutic strategy for neuroprotection. Vascular factors have been suggested to play an important role in glaucoma development and progression. Previously, we have proven the neuroprotective effects of pituitary adenylate-cyclase-activating polypeptide (PACAP) eye drops in an inducible, microbeads model in rats that is able to reproduce many clinically relevant features of human glaucoma. In the present study, we examined the potential protective effects of PACAP1-38 on the retinal vasculature and the molecular changes in hypoxia. Ocular hypertension was induced by injection of microbeads into the anterior chamber, while control rats received PBS. PACAP dissolved in vehicle (1 µg/drop) or vehicle treatment was started one day after the injections for four weeks three times a day. Retinal degeneration was assessed with optical coherence tomography (OCT), and vascular and molecular changes were assessed by immunofluorescence labeling. HIF1-α and VEGF-A protein levels were measured by Western blot. OCT images proved severe retinal degeneration in the glaucomatous group, while PACAP1-38 eye drops had a retinoprotective effect. Vascular parameters were deteriorated and molecular analysis suggested hypoxic conditions in glaucoma. PACAP treatment exerted a positive effect against these alterations. In summary, PACAP could prevent the severe damage to the retina and its vasculature induced by ocular hypertension in a microbeads model.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Tóth, Gábor/0000-0002-3604-4385; Atlasz, Tamás/0000-0002-8112-8633}
}

@article{MTMT:34043894,
	title = {Light-Fueled Primitive Replication and Selection in Biomimetic Chemical Systems},
	url = {https://m2.mtmt.hu/api/publication/34043894},
	author = {Bartus, Éva and Tököli, Attila and Mag, Beáta Zsófia and Bajcsi, Áron and Kecskeméti, Gábor and Wéber, Edit and Kele, Zoltán and Fenteany, Gabriel and Martinek, Tamás},
	doi = {10.1021/jacs.3c03597},
	journal-iso = {J AM CHEM SOC},
	journal = {JOURNAL OF THE AMERICAN CHEMICAL SOCIETY},
	volume = {145},
	unique-id = {34043894},
	issn = {0002-7863},
	abstract = {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.},
	keywords = {PEPTIDES; DRIVEN},
	year = {2023},
	eissn = {1520-5126},
	pages = {13371-13383},
	orcid-numbers = {Bartus, Éva/0000-0001-9976-6978; Tököli, Attila/0000-0001-8413-3182; Kecskeméti, Gábor/0000-0002-5584-6869; Wéber, Edit/0000-0002-5904-0619; Kele, Zoltán/0000-0002-4401-0302; Fenteany, Gabriel/0000-0001-7407-2195; Martinek, Tamás/0000-0003-3168-8066}
}

@article{MTMT:34043893,
	title = {Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2},
	url = {https://m2.mtmt.hu/api/publication/34043893},
	author = {Váradi, Györgyi and Kele, Zoltán and Czajlik, András and Borics, Attila and Bende, Gábor and Papp, Csaba Gergő and Rákhely, Gábor and Tóth, Gábor and Batta, Gyula and Galgóczi, László Norbert},
	doi = {10.1002/pro.4692},
	journal-iso = {PROTEIN SCI},
	journal = {PROTEIN SCIENCE},
	volume = {32},
	unique-id = {34043893},
	issn = {0961-8368},
	abstract = {As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond-stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Aspergillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity. However, in the lack of tryptic and chymotryptic proteolytic sites in the ACNCPNNCK sequence, the determination of the disulfide linkage pattern of NFAP2 is not easy with traditional mass spectrometry-based methods. According to in silico predictions working with a preliminary nuclear magnetic resonance (NMR) solution structure, two disulfide isomers of NFAP2 (abbacc and abbcac) were possible. Both were chemically synthesized; and comparative reversed-phase high-performance liquid chromatography, electronic circular dichroism and NMR spectroscopy analyses, and antifungal susceptibility and efficacy tests indicated that the abbcac is the native pattern. This knowledge allowed rational modification of NAFP2 to improve the antifungal efficacy and spectrum through the modulation of the evolutionarily conserved gamma-core region, which is responsible for the activity of several antimicrobial peptides. Disruption of the steric structure of NFAP2 upon gamma-core modification led to the conclusions that this motif may affect the formation of the biologically active three-dimensional structure, and that the gamma-core modulation is not an efficient tool to improve the antifungal efficacy or to change the antifungal spectrum of NFAP2.},
	keywords = {DYNAMICS; PREDICTION; DRUG DESIGN; BONDS; protein structure; ANTIFUNGAL PROTEIN; disulfide linkage pattern},
	year = {2023},
	eissn = {1469-896X},
	orcid-numbers = {Váradi, Györgyi/0000-0001-7907-8908; Kele, Zoltán/0000-0002-4401-0302; Papp, Csaba Gergő/0000-0003-4450-0667; Rákhely, Gábor/0000-0003-2557-3641; Tóth, Gábor/0000-0002-3604-4385; Batta, Gyula/0000-0002-0442-1828; Galgóczi, László Norbert/0000-0002-6976-8910}
}

@article{MTMT:34030642,
	title = {Alzheimer-kór: le tudjuk-e lassítani a betegséget, lesz-e oki terápia?},
	url = {https://m2.mtmt.hu/api/publication/34030642},
	author = {Penke, Botond and Szűcs, Mária and Bogár, Ferenc},
	journal-iso = {BIOKÉMIA},
	journal = {BIOKÉMIA: A MAGYAR BIOKÉMIAI EGYESÜLET FOLYÓIRATA},
	volume = {47},
	unique-id = {34030642},
	issn = {0133-8455},
	year = {2023},
	eissn = {2060-8152},
	pages = {10-29},
	orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Bogár, Ferenc/0000-0002-0611-1452}
}

@article{MTMT:33712712,
	title = {Structural Adaptation of the Single-Stranded DNA-Binding Protein C-Terminal to DNA Metabolizing Partners Guides Inhibitor Design},
	url = {https://m2.mtmt.hu/api/publication/33712712},
	author = {Tököli, Attila and Bodnár, Brigitta and Bogár, Ferenc and Paragi, Gábor and Hetényi, Anasztázia and Bartus, Éva and Wéber, Edit and Hegedüs, Zsófia and Szabó, Zoltán and Kecskeméti, Gábor and Szakonyi, Gerda and Martinek, Tamás},
	doi = {10.3390/pharmaceutics15041032},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {15},
	unique-id = {33712712},
	issn = {1999-4923},
	abstract = {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.},
	year = {2023},
	eissn = {1999-4923},
	orcid-numbers = {Tököli, Attila/0000-0001-8413-3182; Bogár, Ferenc/0000-0002-0611-1452; Paragi, Gábor/0000-0001-5408-1748; Hetényi, Anasztázia/0000-0001-8080-6992; Bartus, Éva/0000-0001-9976-6978; Wéber, Edit/0000-0002-5904-0619; Hegedüs, Zsófia/0000-0002-5546-8167; Szabó, Zoltán/0000-0001-8278-8038; Kecskeméti, Gábor/0000-0002-5584-6869; Szakonyi, Gerda/0000-0002-4366-4283; Martinek, Tamás/0000-0003-3168-8066}
}

@article{MTMT:33702944,
	title = {New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease},
	url = {https://m2.mtmt.hu/api/publication/33702944},
	author = {Penke, Botond and Szűcs, Mária and Bogár, Ferenc},
	doi = {10.3390/ijms24065383},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33702944},
	issn = {1661-6596},
	abstract = {Alzheimer’s disease (AD) is an incurable, progressive neurodegenerative disorder. AD is a complex and multifactorial disease that is responsible for 60–80% of dementia cases. Aging, genetic factors, and epigenetic changes are the main risk factors for AD. Two aggregation-prone proteins play a decisive role in AD pathogenesis: β-amyloid (Aβ) and hyperphosphorylated tau (pTau). Both of them form deposits and diffusible toxic aggregates in the brain. These proteins are the biomarkers of AD. Different hypotheses have tried to explain AD pathogenesis and served as platforms for AD drug research. Experiments demonstrated that both Aβ and pTau might start neurodegenerative processes and are necessary for cognitive decline. The two pathologies act in synergy. Inhibition of the formation of toxic Aβ and pTau aggregates has been an old drug target. Recently, successful Aβ clearance by monoclonal antibodies has raised new hopes for AD treatments if the disease is detected at early stages. More recently, novel targets, e.g., improvements in amyloid clearance from the brain, application of small heat shock proteins (Hsps), modulation of chronic neuroinflammation by different receptor ligands, modulation of microglial phagocytosis, and increase in myelination have been revealed in AD research.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Penke, Botond/0000-0003-0938-0567; Bogár, Ferenc/0000-0002-0611-1452}
}

@article{MTMT:33676645,
	title = {Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP},
	url = {https://m2.mtmt.hu/api/publication/33676645},
	author = {Váradi, Györgyi and Batta, Gyula and Galgóczi, László Norbert and Hajdu, Dorottya Zsuzsanna and Fizil, Ádám and Czajlik, András and Virágh, Máté and Kele, Zoltán and Meyer, Vera and Jung, Sascha and Marx, Florentine and Tóth, Gábor},
	doi = {10.1021/acs.jnatprod.2c00954},
	journal-iso = {J NAT PROD},
	journal = {JOURNAL OF NATURAL PRODUCTS},
	volume = {86},
	unique-id = {33676645},
	issn = {0163-3864},
	abstract = {Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation. The native protein was synthesized via oxidative folding with uniform protection for cysteine thiols. AFP's biological activity depends heavily on the pattern of natural disulfide bonds. Enzymatic digestion and MS analysis provide proof for interlocking disulfide topology (abcdabcd) that was previously assumed. With this knowledge, a semi-orthogonal thiol protection method was designed. By following this strategy, out of a possible 105, only 6 disulfide isomers formed and 1 of them proved to be identical with the native protein. This approach allows the synthesis of analogs for examining structure-activity relationships and, thus, preparing AFP variants with higher antifungal activity.},
	year = {2023},
	eissn = {1520-6025},
	pages = {782-790},
	orcid-numbers = {Váradi, Györgyi/0000-0001-7907-8908; Batta, Gyula/0000-0002-0442-1828; Galgóczi, László Norbert/0000-0002-6976-8910; Fizil, Ádám/0000-0002-4815-5744; Virágh, Máté/0000-0002-2278-1288; Kele, Zoltán/0000-0002-4401-0302; Meyer, Vera/0000-0002-2298-2258; Tóth, Gábor/0000-0002-3604-4385}
}

@article{MTMT:33611580,
	title = {Enhanced Antibacterial Activity of Substituted Derivatives of NCR169C Peptide},
	url = {https://m2.mtmt.hu/api/publication/33611580},
	author = {Howan, Dian Herlinda Octorina and Jenei, Sándor and Szolomájer, János and Endre, Gabriella and Kondorosi, Éva and Tóth, Gábor},
	doi = {10.3390/ijms24032694},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33611580},
	issn = {1661-6596},
	abstract = {Medicago truncatula in symbiosis with its rhizobial bacterium partner produces more than 700 nodule-specific cysteine-rich (NCR) peptides with diverse physicochemical properties. Most of the cationic NCR peptides have antimicrobial activity and the potential to tackle antimicrobial resistance with their novel modes of action. This work focuses on the antibacterial activity of the NCR169 peptide derivatives as we previously demonstrated that the C-terminal sequence of NCR169 (NCR169C17–38) has antifungal activity, affecting the viability, morphology, and biofilm formation of various Candida species. Here, we show that NCR169C17–38 and its various substituted derivatives are also able to kill ESKAPE pathogens such as Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. The replacement of the two cysteines with serines enhanced the antimicrobial activity against most of the tested bacteria, indicating that the formation of a disulfide bridge is not required. As tryptophan can play role in the interaction with bacterial membranes and thus in antibacterial activity, we replaced the tryptophans in the NCR169C17–38C12,17/S sequence with various modified tryptophans, namely 5-methyl tryptophan, 5-fluoro tryptophan, 6-fluoro tryptophan, 7-aza tryptophan, and 5-methoxy tryptophan, in the synthesis of NCR169C17–38C12,17/S analogs. The results demonstrate that the presence of modified fluorotryptophans can significantly enhance the antimicrobial activity without notable hemolytic effect, and this finding could be beneficial for the further development of new AMPs from the members of the NCR peptide family.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Szolomájer, János/0000-0003-1458-6156; Endre, Gabriella/0000-0001-9493-7395; Kondorosi, Éva/0000-0002-4065-8515; Tóth, Gábor/0000-0002-3604-4385}
}