@article{MTMT:34722791,
	title = {A synthetic flavonoid derivate in the plasma membrane transforms the voltage‐clamp fluorometry signal of CiHv1},
	url = {https://m2.mtmt.hu/api/publication/34722791},
	author = {Pethő, Zoltán Dénes and Pajtás, Dávid and Piga, Martina and Magyar, Zsuzsanna Édua and Zákány, Florina and Kovács, Tamás and Zidar, Nace and Panyi, György and Varga, Zoltán and Papp, Ferenc},
	doi = {10.1111/febs.17105},
	journal-iso = {FEBS J},
	journal = {FEBS JOURNAL},
	unique-id = {34722791},
	issn = {1742-464X},
	abstract = {Voltage‐clamp fluorometry (VCF) enables the study of voltage‐sensitive proteins through fluorescent labeling accompanied by ionic current measurements for voltage‐gated ion channels. The heterogeneity of the fluorescent signal represents a significant challenge in VCF. The VCF signal depends on where the cysteine mutation is incorporated, making it difficult to compare data among different mutations and different studies and standardize their interpretation. We have recently shown that the VCF signal originates from quenching amino acids in the vicinity of the attached fluorophores, together with the effect of the lipid microenvironment. Based on these, we performed experiments to test the hypothesis that the VCF signal could be altered by amphiphilic quenching molecules in the cell membrane. Here we show that a phenylalanine‐conjugated flavonoid (4‐oxo‐2‐phenyl‐4H‐chromene‐7‐yl)‐phenylalanine, (later Oxophench) has potent effects on the VCF signals of the Ciona intestinalis H V 1 (CiHv1) proton channel. Using spectrofluorimetry, we showed that Oxophench quenches TAMRA (5(6)‐carboxytetramethylrhodamine‐(methane thiosulfonate)) fluorescence. Moreover, Oxophench reduces the baseline fluorescence in oocytes and incorporates into the cell membrane while reducing the membrane fluidity of HEK293 cells. Our model calculations confirmed that Oxophench, a potent membrane‐bound quencher, modifies the VCF signal during conformational changes. These results support our previously published model of VCF signal generation and point out that a change in the VCF signal may not necessarily indicate an altered conformational transition of the investigated protein.},
	year = {2024},
	eissn = {1742-4658},
	orcid-numbers = {Piga, Martina/0009-0006-8549-3386; Kovács, Tamás/0000-0002-1084-9847; Panyi, György/0000-0001-6227-3301}
}

@article{MTMT:34037015,
	title = {Effect of the Lipid Landscape on the Efficacy of Cell-Penetrating Peptides},
	url = {https://m2.mtmt.hu/api/publication/34037015},
	author = {Zákány, Florina and Mándity, István and Varga, Zoltán and Panyi, György and Nagy, Péter and Kovács, Tamás},
	doi = {10.3390/cells12131700},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {12},
	unique-id = {34037015},
	abstract = {Every cell biological textbook teaches us that the main role of the plasma membrane is to separate cells from their neighborhood to allow for a controlled composition of the intracellular space. The mostly hydrophobic nature of the cell membrane presents an impenetrable barrier for most hydrophilic molecules larger than 1 kDa. On the other hand, cell-penetrating peptides (CPPs) are capable of traversing this barrier without compromising membrane integrity, and they can do so on their own or coupled to cargos. Coupling biologically and medically relevant cargos to CPPs holds great promise of delivering membrane-impermeable drugs into cells. If the cargo is able to interact with certain cell types, uptake of the CPP–drug complex can be tailored to be cell-type-specific. Besides outlining the major membrane penetration pathways of CPPs, this review is aimed at deciphering how properties of the membrane influence the uptake mechanisms of CPPs. By summarizing an extensive body of experimental evidence, we argue that a more ordered, less flexible membrane structure, often present in the very diseases planned to be treated with CPPs, decreases their cellular uptake. These correlations are not only relevant for understanding the cellular biology of CPPs, but also for rationally improving their value in translational or clinical applications.},
	year = {2023},
	eissn = {2073-4409},
	orcid-numbers = {Mándity, István/0000-0003-2865-6143; Panyi, György/0000-0001-6227-3301; Nagy, Péter/0000-0002-7466-805X; Kovács, Tamás/0000-0002-1084-9847}
}

@article{MTMT:33671944,
	title = {Veklury® (remdesivir) formulations inhibit initial membrane‐coupled events of SARS‐CoV‐2 infection due to their sulfobutylether‐β‐cyclodextrin content},
	url = {https://m2.mtmt.hu/api/publication/33671944},
	author = {Kovács, Tamás and Kurtan, Kitti and Varga, Zoltán and Nagy, Péter and Panyi, György and Zákány, Florina},
	doi = {10.1111/bph.16063},
	journal-iso = {BR J PHARMACOL},
	journal = {BRITISH JOURNAL OF PHARMACOLOGY},
	volume = {180},
	unique-id = {33671944},
	issn = {0007-1188},
	abstract = {Background and Purpose: Despite its contradictory clinical performance, remdesivir (Veklury®) has a pivotal role in COVID-19 therapy. Possible contributions of the vehicle, sulfobutylether-β-cyclodextrin (SBECD) to Veklury® effects have been overlooked. The powder and solution formulations of Veklury® are treated equivalently despite their different vehicle content. Our objective was to study Veklury® effects on initial membrane-coupled events of SARS-CoV-2 infection focusing on the cholesterol depletion-mediated role of SBECD. Experimental Approach: Using time-correlated flow cytometry and quantitative three-dimensional confocal microscopy, we studied early molecular events of SARS-CoV-2–host cell membrane interactions. Key Results: Veklury® and different cholesterol-depleting cyclodextrins (CDs) reduced binding of the spike receptor-binding domain (RBD) to ACE2 and spike trimer internalization for Wuhan-Hu-1, Delta and Omicron variants. Correlations of these effects with cholesterol-dependent changes in membrane structure and decreased lipid raft-dependent ACE2–TMPRSS2 interaction establish that SBECD is not simply a vehicle but also an effector along with remdesivir due to its cholesterol-depleting potential. Veklury® solution inhibited RBD binding more efficiently due to its twice higher SBECD content. The CD-induced inhibitory effects were more prominent at lower RBD concentrations and in cells with lower endogenous ACE2 expression, indicating that the supportive CD actions can be even more pronounced during in vivo infection when viral load and ACE expression are typically low. Conclusion and Implications: Our findings call for the differentiation of Veklury® formulations in meta-analyses of clinical trials, potentially revealing neglected benefits of the solution formulation, and also raise the possibility of adjuvant cyclodextrin (CD) therapy, even at higher doses, in COVID-19.},
	year = {2023},
	eissn = {1476-5381},
	pages = {2064-2084},
	orcid-numbers = {Kovács, Tamás/0000-0002-1084-9847; Nagy, Péter/0000-0002-7466-805X; Panyi, György/0000-0001-6227-3301}
}

@article{MTMT:33274154,
	title = {Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?},
	url = {https://m2.mtmt.hu/api/publication/33274154},
	author = {Kovács, Tamás and Nagy, Péter and Panyi, György and Szente, Lajos and Varga, Zoltán and Zákány, Florina},
	doi = {10.3390/pharmaceutics14122559},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {14},
	unique-id = {33274154},
	issn = {1999-4923},
	abstract = {Cyclodextrins, representing a versatile family of cyclic oligosaccharides, have extensive pharmaceutical applications due to their unique truncated cone-shaped structure with a hydrophilic outer surface and a hydrophobic cavity, which enables them to form non-covalent host–guest inclusion complexes in pharmaceutical formulations to enhance the solubility, stability and bioavailability of numerous drug molecules. As a result, cyclodextrins are mostly considered as inert carriers during their medical application, while their ability to interact not only with small molecules but also with lipids and proteins is largely neglected. By forming inclusion complexes with cholesterol, cyclodextrins deplete cholesterol from cellular membranes and thereby influence protein function indirectly through alterations in biophysical properties and lateral heterogeneity of bilayers. In this review, we summarize the general chemical principles of direct cyclodextrin–protein interactions and highlight, through relevant examples, how these interactions can modify protein functions in vivo, which, despite their huge potential, have been completely unexploited in therapy so far. Finally, we give a brief overview of disorders such as Niemann–Pick type C disease, atherosclerosis, Alzheimer’s and Parkinson’s disease, in which cyclodextrins already have or could have the potential to be active therapeutic agents due to their cholesterol-complexing or direct protein-targeting properties.},
	year = {2022},
	eissn = {1999-4923},
	orcid-numbers = {Nagy, Péter/0000-0002-7466-805X; Panyi, György/0000-0001-6227-3301; Szente, Lajos/0000-0002-7734-5440}
}

@{MTMT:32837794,
	title = {Cyclodextrins as promising therapeutics against cholesterol overload},
	url = {https://m2.mtmt.hu/api/publication/32837794},
	author = {Zákány, Florina and Kovács, Tamás and Szente, Lajos and Varga, Zoltán},
	booktitle = {Cholesterol},
	doi = {10.1016/B978-0-323-85857-1.00028-6},
	unique-id = {32837794},
	year = {2022},
	pages = {927-967}
}

@article{MTMT:32673363,
	title = {It Takes More than Two to Tango: Complex, Hierarchal, and Membrane-Modulated Interactions in the Regulation of Receptor Tyrosine Kinases},
	url = {https://m2.mtmt.hu/api/publication/32673363},
	author = {Kovács, Tamás and Zákány, Florina and Nagy, Péter},
	doi = {10.3390/cancers14040944},
	journal-iso = {CANCERS},
	journal = {CANCERS},
	volume = {14},
	unique-id = {32673363},
	year = {2022},
	eissn = {2072-6694},
	pages = {944},
	orcid-numbers = {Kovács, Tamás/0000-0002-1084-9847; Nagy, Péter/0000-0002-7466-805X}
}

@article{MTMT:32523431,
	title = {Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells},
	url = {https://m2.mtmt.hu/api/publication/32523431},
	author = {Csomós, István and Nagy, Péter and Filep, Csenge Boróka and Rebenku, István and Nizsalóczki, Enikő and Kovács, Tamás and Vámosi, György and Mátyus, László and Bodnár, Andrea},
	doi = {10.3390/ijms222312974},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {32523431},
	issn = {1661-6596},
	year = {2021},
	eissn = {1422-0067},
	orcid-numbers = {Nagy, Péter/0000-0002-7466-805X; Kovács, Tamás/0000-0002-1084-9847; Bodnár, Andrea/0000-0002-9610-4589}
}

@article{MTMT:32510829,
	title = {Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction},
	url = {https://m2.mtmt.hu/api/publication/32510829},
	author = {Kovács, Tamás and Sohajda, Tamás and Szente, Lajos and Nagy, Péter and Panyi, György and Varga, Zoltán and Zákány, Florina},
	doi = {10.3389/fmolb.2021.735357},
	journal-iso = {FRONT MOL BIOSCI},
	journal = {FRONTIERS IN MOLECULAR BIOSCIENCES},
	volume = {8},
	unique-id = {32510829},
	year = {2021},
	eissn = {2296-889X},
	orcid-numbers = {Kovács, Tamás/0000-0002-1084-9847; Nagy, Péter/0000-0002-7466-805X; Panyi, György/0000-0001-6227-3301}
}

@article{MTMT:32219377,
	title = {An omega-3, but Not an omega-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin},
	url = {https://m2.mtmt.hu/api/publication/32219377},
	author = {Zákány, Florina and Szabó, Máté and Batta, Gyula Gábor (Ifj.) and Kárpáti, Levente and Mándity, István and Fülöp, Péter and Varga, Zoltán and Panyi, György and Nagy, Péter and Kovács, Tamás},
	doi = {10.3389/fcell.2021.647300},
	journal-iso = {FRONT CELL DEV BIOL},
	journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY},
	volume = {9},
	unique-id = {32219377},
	issn = {2296-634X},
	abstract = {Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and omega-6 gamma-linolenic acid (GLA) increase, while omega-3 alpha-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity. Pretreatment with ALA counteracts, while SA or GLA enhances cholesterol-induced DP elevations. Furthermore, ALA (but not SA or GLA) increases endo-lysosomal escape of penetratin, a cell-penetrating peptide. In summary, we have developed a novel method to measure DP in large quantities of individual living cells and propose ALA as a physiological DP lowering agent facilitating cytoplasmic entry of penetratin.},
	keywords = {Flow Cytometry; cholesterol; PENETRATIN; Polyunsaturated fatty acids; Membrane dipole potential},
	year = {2021},
	eissn = {2296-634X},
	orcid-numbers = {Batta, Gyula Gábor (Ifj.)/0000-0001-8735-6920; Kárpáti, Levente/0000-0002-9091-3027; Mándity, István/0000-0003-2865-6143; Panyi, György/0000-0001-6227-3301; Nagy, Péter/0000-0002-7466-805X; Kovács, Tamás/0000-0002-1084-9847}
}

@article{MTMT:31996377,
	title = {Statin‐boosted cellular uptake and endosomal escape of penetratin due to reduced membrane dipole potential},
	url = {https://m2.mtmt.hu/api/publication/31996377},
	author = {Batta, Gyula Gábor (Ifj.) and Kárpáti, Levente and Henrique, Gabriela Fulaneto and Tóth, Gabriella and Tarapcsák, Szabolcs and Kovács, Tamás and Zákány, Florina and Mándity, István and Nagy, Péter},
	doi = {10.1111/bph.15509},
	journal-iso = {BR J PHARMACOL},
	journal = {BRITISH JOURNAL OF PHARMACOLOGY},
	volume = {178},
	unique-id = {31996377},
	issn = {0007-1188},
	year = {2021},
	eissn = {1476-5381},
	pages = {3667-3681},
	orcid-numbers = {Batta, Gyula Gábor (Ifj.)/0000-0001-8735-6920; Kárpáti, Levente/0000-0002-9091-3027; Kovács, Tamás/0000-0002-1084-9847; Mándity, István/0000-0003-2865-6143; Nagy, Péter/0000-0002-7466-805X}
}