@article{MTMT:34767238, title = {Examinations of cellular uptake of cell penetrating peptides in vitro and in vivo}, url = {https://m2.mtmt.hu/api/publication/34767238}, author = {Toth, Gabriella and Batta, Gyula Gábor (Ifj.) and Karpati, Levente and Szöőr, Árpád and Mandity, Istvan and Nagy, Péter}, journal-iso = {EUR BIOPHYS J}, journal = {EUROPEAN BIOPHYSICS JOURNAL}, volume = {52}, unique-id = {34767238}, issn = {0175-7571}, year = {2023}, eissn = {1432-1017}, pages = {S163-S163}, orcid-numbers = {Batta, Gyula Gábor (Ifj.)/0000-0001-8735-6920; Nagy, Péter/0000-0002-7466-805X} } @article{MTMT:34766294, title = {Effect of Erbb2 Missense Mutations on Dimer Formation}, url = {https://m2.mtmt.hu/api/publication/34766294}, author = {Serrano Cano, Tayde Gabriela and Yasari, Atena and Tiemann-Boege, Irene and Nagy, Péter}, journal-iso = {EUR BIOPHYS J}, journal = {EUROPEAN BIOPHYSICS JOURNAL}, volume = {52}, unique-id = {34766294}, issn = {0175-7571}, year = {2023}, eissn = {1432-1017}, pages = {S105-S105}, orcid-numbers = {Nagy, Péter/0000-0002-7466-805X} } @article{MTMT:34764950, title = {Probes for Single-Molecule Microscopy Analysis of ErbB4 Biophysical Properties}, url = {https://m2.mtmt.hu/api/publication/34764950}, author = {Kalouskova, Barbora and Serrano Cano, Tayde Gabriela and Nagy, Péter and Brameshuber, Mario}, journal-iso = {EUR BIOPHYS J}, journal = {EUROPEAN BIOPHYSICS JOURNAL}, volume = {52}, unique-id = {34764950}, issn = {0175-7571}, year = {2023}, eissn = {1432-1017}, pages = {S87-S87}, orcid-numbers = {Nagy, Péter/0000-0002-7466-805X} } @article{MTMT:34089348, title = {Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition}, url = {https://m2.mtmt.hu/api/publication/34089348}, author = {Ujlaki, Gyula and Kovács, Tünde and Vida, András and Kókai, Endre and Rauch, Boglárka and Schwarcz, Szandra and Mikó, Edit and Janka, Eszter and Sipos, Adrienn and Hegedűs, Csaba and Uray (Davis), Karen L. and Nagy, Péter and Bay, Péter}, doi = {10.3390/molecules28155898}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {28}, unique-id = {34089348}, issn = {1420-3049}, abstract = {Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties. We constructed a 30-member bacterial metabolite library and screened the library compounds for effects on cell proliferation and epithelial-mesenchymal transition. The metabolites were applied to 4T1 murine breast cancer cells in concentrations corresponding to the reference serum concentrations. However, yric acid, glycolic acid, d-mannitol, 2,3-butanediol, and trans-ferulic acid exerted cytostatic effects, and 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and vanillic acid exerted hyperproliferative effects. Furthermore, 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 2,3-butanediol, and hydrocinnamic acid inhibited epithelial-to-mesenchymal (EMT) transition. We identified redox sets among the metabolites (d-mannitol—d-mannose, 1-butanol—butyric acid, ethylene glycol—glycolic acid—oxalic acid), wherein only one partner within the set (d-mannitol, butyric acid, glycolic acid) possessed bioactivity in our system, suggesting that changes to the local redox potential may affect the bacterial secretome. Of the nine bioactive metabolites, 2,3-butanediol was the only compound with both cytostatic and anti-EMT properties.}, year = {2023}, eissn = {1420-3049}, orcid-numbers = {Janka, Eszter/0000-0003-0724-5281; Nagy, Péter/0000-0002-7466-805X} } @article{MTMT:34068193, title = {Isolation and Micromass Culturing of Primary Chicken Chondroprogenitor Cells for Cartilage Regeneration}, url = {https://m2.mtmt.hu/api/publication/34068193}, author = {Takács, Roland and Juhász, Tamás and Katona, Éva and Szucs-Somogyi, Csilla and Vágó, Judit and Hajdú, Tibor and Bíróné Barna, Krisztina and Nagy, Péter and Zákány, Róza and Matta, Csaba}, doi = {10.1002/cpz1.835}, journal-iso = {CURR PROT}, journal = {CURRENT PROTOCOLS}, volume = {3}, unique-id = {34068193}, issn = {2691-1299}, year = {2023}, pages = {1-29}, orcid-numbers = {Nagy, Péter/0000-0002-7466-805X; Matta, Csaba/0000-0002-9678-7420} } @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:33786991, title = {Improved estimation of the ratio of detection efficiencies of excited acceptors and donors for FRET measurements}, url = {https://m2.mtmt.hu/api/publication/33786991}, author = {Batta, Ágnes and Hajdu, Tímea and Nagy, Péter}, doi = {10.1002/cyto.a.24728}, journal-iso = {CYTOM PART A}, journal = {CYTOMETRY PART A}, volume = {103}, unique-id = {33786991}, issn = {1552-4922}, abstract = {Forster resonance energy transfer (FRET) is a radiationless interaction between a donor and an acceptor whose distance dependence makes it a sensitive tool for studying the oligomerization and the structure of proteins. When FRET is determined by measuring the sensitized emission of the acceptor, a parameter characterizing the ratio of detection efficiencies of an excited acceptor versus an excited donor is invariably involved in the formalism. For FRET measurements involving fluorescent antibodies or other external labels, this parameter, designated by alpha, is usually determined by comparing the intensity of a known number of donors and acceptors in two independent samples leading to a large statistical variability if the sample size is small. Here, we present a method that improves precision by applying microbeads with a calibrated number of antibody binding sites and a donor-acceptor mixture in which donors and acceptors are present in a certain, experimentally determined ratio. A formalism is developed for determining alpha and the superior reproducibility of the proposed method compared to the conventional approach is demonstrated. Since the novel methodology does not require sophisticated calibration samples or special instrumentation, it can be widely applied for the quantification of FRET experiments in biological research.}, keywords = {FRET; CALIBRATION; Fluorescence microscopy}, year = {2023}, eissn = {1552-4930}, pages = {563-574}, orcid-numbers = {Nagy, Péter/0000-0002-7466-805X} } @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:33538163, title = {Cell-Penetrating Dabcyl-Containing Tetraarginines with Backbone Aromatics as Uptake Enhancers}, url = {https://m2.mtmt.hu/api/publication/33538163}, author = {Yousef, M. and Szabó, Ildikó and Murányi, József and Illien, Françoise and Soltész, Dóra and Bató, Csaba and Tóth, Gabriella and Batta, Gyula Gábor (Ifj.) and Nagy, Péter and Sagan, Sandrine and Bánóczi, Zoltán}, doi = {10.3390/pharmaceutics15010141}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {15}, unique-id = {33538163}, issn = {1999-4923}, abstract = {Cell-penetrating peptides represent an emerging class of carriers capable of effective cellular delivery. This work demonstrates the preparation and investigation of efficient CPPs. We have already shown that the presence of 4-((4-(dimethylamino)phenyl)azo)benzoic acid (Dabcyl) and Trp greatly increase the uptake of oligoarginines. This work is a further step in that direction. We have explored the possibility of employing unnatural, aromatic amino acids, to mimic Trp properties and effects. The added residues allow the introduction of aromaticity, not as a side-chain group, but rather as a part of the sequence. The constructs presented exceptional internalization on various cell lines, with an evident structure–activity relationship. The CPPs were investigated for their entry mechanisms, and our peptides exploit favorable pathways, yet one of the peptides relies highly on direct penetration. Confocal microscopy studies have shown selectivity towards the cell lines, by showing diffuse uptake in FADU cells, while vesicular uptake takes place in SCC-25 cell line. These highly active CPPs have proved their applicability in cargo delivery by successfully delivering antitumor drugs into MCF-7 and MDA-MB-231 cells. The modifications in the sequences allow the preparation of short yet highly effective constructs able to rival the penetration of well-known CPPs such as octaarginine (Arg8).}, year = {2023}, eissn = {1999-4923}, orcid-numbers = {Szabó, Ildikó/0000-0002-9844-7841; Murányi, József/0000-0001-5672-6482; Batta, Gyula Gábor (Ifj.)/0000-0001-8735-6920; Nagy, Péter/0000-0002-7466-805X; Bánóczi, Zoltán/0000-0003-1880-4042} } @article{MTMT:33561152, title = {Principles of Resonance Energy Transfer}, url = {https://m2.mtmt.hu/api/publication/33561152}, author = {Szabó, Ágnes Tímea and Szöllősi, János and Nagy, Péter}, doi = {10.1002/cpz1.625}, journal-iso = {CURR PROT}, journal = {CURRENT PROTOCOLS}, volume = {2}, unique-id = {33561152}, issn = {2691-1299}, abstract = {This unit describes the basic principles of Förster resonance energy transfer (FRET). Beginning with a brief summary of the history of FRET applications, the theory of FRET is introduced in detail using figures to explain all the important parameters of the FRET process. After listing various approaches for measuring FRET efficiency, several pieces of advice are given on choosing the appropriate instrumentation. The unit concludes with a discussion of the limitations of FRET measurements followed by a few examples of the latest FRET applications, including new developments such as spectral flow cytometric FRET, single-molecule FRET, and combinations of FRET with super-resolution or lifetime imaging microscopy and with molecular dynamics simulations. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. This article was corrected on 20 December 2022. See the end of the full text for details. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.}, year = {2022}, orcid-numbers = {Nagy, Péter/0000-0002-7466-805X} }