TY - JOUR AU - Toth, Gabriella AU - Batta, Gyula Gábor (Ifj.) AU - Karpati, Levente AU - Szöőr, Árpád AU - Mandity, Istvan AU - Nagy, Péter TI - Examinations of cellular uptake of cell penetrating peptides in vitro and in vivo JF - EUROPEAN BIOPHYSICS JOURNAL J2 - EUR BIOPHYS J VL - 52 PY - 2023 IS - S1 SP - S163 EP - S163 SN - 0175-7571 UR - https://m2.mtmt.hu/api/publication/34767238 ID - 34767238 LA - English DB - MTMT ER - TY - JOUR AU - Serrano Cano, Tayde Gabriela AU - Yasari, Atena AU - Tiemann-Boege, Irene AU - Nagy, Péter TI - Effect of Erbb2 Missense Mutations on Dimer Formation JF - EUROPEAN BIOPHYSICS JOURNAL J2 - EUR BIOPHYS J VL - 52 PY - 2023 IS - S1 SP - S105 EP - S105 SN - 0175-7571 UR - https://m2.mtmt.hu/api/publication/34766294 ID - 34766294 LA - English DB - MTMT ER - TY - JOUR AU - Kalouskova, Barbora AU - Serrano Cano, Tayde Gabriela AU - Nagy, Péter AU - Brameshuber, Mario TI - Probes for Single-Molecule Microscopy Analysis of ErbB4 Biophysical Properties JF - EUROPEAN BIOPHYSICS JOURNAL J2 - EUR BIOPHYS J VL - 52 PY - 2023 IS - S1 SP - S87 EP - S87 SN - 0175-7571 UR - https://m2.mtmt.hu/api/publication/34764950 ID - 34764950 LA - English DB - MTMT ER - TY - JOUR AU - Ujlaki, Gyula AU - Kovács, Tünde AU - Vida, András AU - Kókai, Endre AU - Rauch, Boglárka AU - Schwarcz, Szandra AU - Mikó, Edit AU - Janka, Eszter AU - Sipos, Adrienn AU - Hegedűs, Csaba AU - Uray (Davis), Karen L. AU - Nagy, Péter AU - Bay, Péter TI - Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 15 SN - 1420-3049 DO - 10.3390/molecules28155898 UR - https://m2.mtmt.hu/api/publication/34089348 ID - 34089348 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Takács, Roland AU - Juhász, Tamás AU - Katona, Éva AU - Szucs-Somogyi, Csilla AU - Vágó, Judit AU - Hajdú, Tibor AU - Bíróné Barna, Krisztina AU - Nagy, Péter AU - Zákány, Róza AU - Matta, Csaba TI - Isolation and Micromass Culturing of Primary Chicken Chondroprogenitor Cells for Cartilage Regeneration JF - CURRENT PROTOCOLS J2 - CURR PROT VL - 3 PY - 2023 IS - 7 SP - 1 EP - 29 PG - 29 SN - 2691-1299 DO - 10.1002/cpz1.835 UR - https://m2.mtmt.hu/api/publication/34068193 ID - 34068193 LA - English DB - MTMT ER - TY - JOUR AU - Zákány, Florina AU - Mándity, István AU - Varga, Zoltán AU - Panyi, György AU - Nagy, Péter AU - Kovács, Tamás TI - Effect of the Lipid Landscape on the Efficacy of Cell-Penetrating Peptides JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 13 PG - 29 SN - 2073-4409 DO - 10.3390/cells12131700 UR - https://m2.mtmt.hu/api/publication/34037015 ID - 34037015 N1 - Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, 1085, Hungary TTK Lendület Artificial Transporter Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Budapest, 1117, Hungary Export Date: 16 October 2023 Correspondence Address: Nagy, P.; Department of Biophysics and Cell Biology, Hungary; email: nagyp@med.unideb.hu Correspondence Address: Kovacs, T.; Department of Biophysics and Cell Biology, Hungary; email: kovacs.tamas@med.unideb.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Batta, Ágnes AU - Hajdu, Tímea AU - Nagy, Péter TI - Improved estimation of the ratio of detection efficiencies of excited acceptors and donors for FRET measurements JF - CYTOMETRY PART A J2 - CYTOM PART A VL - 103 PY - 2023 IS - 7 SP - 563 EP - 574 PG - 12 SN - 1552-4922 DO - 10.1002/cyto.a.24728 UR - https://m2.mtmt.hu/api/publication/33786991 ID - 33786991 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Tamás AU - Kurtan, Kitti AU - Varga, Zoltán AU - Nagy, Péter AU - Panyi, György AU - Zákány, Florina TI - Veklury® (remdesivir) formulations inhibit initial membrane‐coupled events of SARS‐CoV‐2 infection due to their sulfobutylether‐β‐cyclodextrin content JF - BRITISH JOURNAL OF PHARMACOLOGY J2 - BR J PHARMACOL VL - 180 PY - 2023 IS - 16 SP - 2064 EP - 2084 PG - 21 SN - 0007-1188 DO - 10.1111/bph.16063 UR - https://m2.mtmt.hu/api/publication/33671944 ID - 33671944 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Yousef, M. AU - Szabó, Ildikó AU - Murányi, József AU - Illien, Françoise AU - Soltész, Dóra AU - Bató, Csaba AU - Tóth, Gabriella AU - Batta, Gyula Gábor (Ifj.) AU - Nagy, Péter AU - Sagan, Sandrine AU - Bánóczi, Zoltán TI - Cell-Penetrating Dabcyl-Containing Tetraarginines with Backbone Aromatics as Uptake Enhancers JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 1 PG - 20 SN - 1999-4923 DO - 10.3390/pharmaceutics15010141 UR - https://m2.mtmt.hu/api/publication/33538163 ID - 33538163 N1 - Department of Organic Chemistry, Eötvös L. University, Budapest, 1117, Hungary MTA-ELTE Research Group of Peptide Chemistry, Eötvös Loránd Research Network (ELKH), Budapest, 1117, Hungary Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, 1094, Hungary MTA-SE, Pathobiochemistry Research Group, Budapest, 1094, Hungary Sorbonne Université, École Normale Supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, Paris, 75005, France Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary Department of Genetics and Applied Microbiology, Faculty of Science and Technology, University of Debrecen, Debrecen, 4032, Hungary Cited By :5 Export Date: 26 January 2024 Correspondence Address: Bánóczi, Z.; Department of Organic Chemistry, Hungary; email: zoltan.banoczi@ttk.elte.hu AB - 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). LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Ágnes Tímea AU - Szöllősi, János AU - Nagy, Péter TI - Principles of Resonance Energy Transfer JF - CURRENT PROTOCOLS J2 - CURR PROT VL - 2 PY - 2022 IS - 12 SN - 2691-1299 DO - 10.1002/cpz1.625 UR - https://m2.mtmt.hu/api/publication/33561152 ID - 33561152 AB - 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. LA - English DB - MTMT ER -