TY - JOUR AU - Vishwakarma, Gayatri AU - Andrási, Melinda AU - Szabó, Dávid Ruben AU - Hajdu, Péter Béla AU - Petrilla, Vladimir AU - Petrillová, Monika AU - Legath, Jaroslav AU - Gáspár, Attila TI - Analysis of intact venom proteins with capillary zone electrophoresis - mass spectrometry JF - MICROCHEMICAL JOURNAL J2 - MICROCHEM J VL - 200 PY - 2024 PG - 8 SN - 0026-265X DO - 10.1016/j.microc.2024.110290 UR - https://m2.mtmt.hu/api/publication/34774200 ID - 34774200 N1 - Department of Inorganic and Analytical Chemistry, University of Debrecen, Egyetem ter 1., Debrecen, 4032, Hungary Department of Dental Biochemistry and Department of Biophysics and Cell Biology, University of Debrecen, Egyetem tér 1., Debrecen, 4032, Hungary Department of Biology and Physiology, University of Veterinary Medicine and Pharmacy, Košice, Slovakia Zoological Department, Zoological Garden Košice, Košice-Kavečany, Slovakia Department of General Competencies, University of Veterinary Medicine and Pharmacy, Košice, Slovakia Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, Košice, Slovakia Department of Biotechnology and Bioinformatics, Faculty of Chemistry, Rzeszow University of Technology, Rzeszow, Poland Export Date: 6 April 2024 CODEN: MICJA Correspondence Address: Gaspar, A.; Department of Inorganic and Analytical Chemistry, Egyetem ter 1., Hungary; email: gaspar@science.unideb.hu Funding details: Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K142134, K128525, 2022_526066, APVV - 22-0101 Funding text 1: The authors acknowledge the financial support provided for this project by the National Research, Development and Innovation Office, Hungary (K142134 (AG), K128525 (HP)), Stipendium Hungaricum (#2022_526066) and by the project APVV-22-0101 (Slovak Research and Development Agency Departmental Organization of the Ministry of Education, Science, Research and Sports of the Slovak Republic). LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Lőrinc AU - Mezősi-Csaplár, Marianna AU - Rebenku, István AU - Vereb, György AU - Szöőr, Árpád TI - Universal CAR T cells targeted to HER2 with a biotin-trastuzumab soluble linker penetrate spheroids and large tumor xenografts that are inherently resistant to trastuzumab mediated ADCC JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 15 PY - 2024 SP - 1664-3224 SN - 1664-3224 DO - 10.3389/fimmu.2024.1365172 UR - https://m2.mtmt.hu/api/publication/34762667 ID - 34762667 AB - CAR T cell therapies face challenges in combating solid tumors due to their single-target approach, which becomes ineffective if the targeted antigen is absent or lost. Universal CAR T cells (UniCAR Ts) provide a promising solution by utilizing molecular tags (linkers), such as biotin conjugated to monoclonal antibodies, enabling them to target a variety of tumor antigens. Recently, we showed that conventional CAR T cells could penetrate the extracellular matrix (ECM) of ADCC-resistant tumors, which forms a barrier to therapeutic antibodies. This finding led us to investigate whether UniCAR T cells, targeted by soluble antibody-derived linkers, could similarly tackle ADCC-resistant tumors where ECM restricts antibody penetration. We engineered UniCAR T cells by incorporating a biotin-binding monomeric streptavidin 2 (mSA2) domain for targeting HER2 via biotinylated trastuzumab (BT). The activation and cytotoxicity of UniCAR T cells in the presence or absence of BT were evaluated in conventional immunoassays. A 3D spheroid coculture was set up to test the capability of UniCAR Ts to access ECM-masked HER2 + cells. For in vivo analysis, we utilized a HER2 + xenograft model in which intravenously administered UniCAR T cells were supplemented with intraperitoneal BT treatments. In vitro , BT-guided UniCAR T cells showed effective activation and distinct anti-tumor response. Upon target recognition, IFNγ secretion correlated with BT concentration. In the presence of BT, UniCAR T cells effectively penetrated HER2 + spheroids and induced cell death in their core regions. In vivo , upon intravenous administration of UniCAR Ts, circulating BT linkers immediately engaged the mSA2 domain and directed effector cells to the HER2 + tumors. However, these co-treated mice died early, possibly due to the lung infiltration of UniCAR T cells that could recognize both native biotin and HER2. Our results suggest that UniCAR T cells guided with soluble linkers present a viable alternative to conventional CAR T cells, especially for patients resistant to antibody therapy and those with solid tumors exhibiting high antigenic variability. Critical to their success, however, is the choice of an appropriate binding domain for the CAR and the corresponding soluble linker, ensuring both efficacy and safety in therapeutic applications. LA - English DB - MTMT ER - TY - JOUR AU - Pethő, Zoltán Dénes AU - Pajtás, Dávid AU - Piga, Martina AU - Magyar, Zsuzsanna Édua AU - Zákány, Florina AU - Kovács, Tamás AU - Zidar, Nace AU - Panyi, György AU - Varga, Zoltán AU - Papp, Ferenc TI - A synthetic flavonoid derivate in the plasma membrane transforms the voltage‐clamp fluorometry signal of CiHv1 JF - FEBS JOURNAL J2 - FEBS J PY - 2024 PG - 18 SN - 1742-464X DO - 10.1111/febs.17105 UR - https://m2.mtmt.hu/api/publication/34722791 ID - 34722791 N1 - Early View AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Jusztus, Vivien AU - Medyouni, Ghofrane AU - Bagosi, Adrienn AU - Lampé, Rudolf AU - Panyi, György AU - Matolay, Orsolya AU - Maka, Eszter AU - Krasznai, Zoárd Tibor AU - Vörös, Orsolya AU - Hajdu, Péter Béla TI - Activity of Potassium Channels in CD8+ T Lymphocytes: Diagnostic and Prognostic Biomarker in Ovarian Cancer? JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 4 SP - 1949 SN - 1661-6596 DO - 10.3390/ijms25041949 UR - https://m2.mtmt.hu/api/publication/34565926 ID - 34565926 AB - CD8+ T cells play a role in the suppression of tumor growth and immunotherapy. Ion channels control the Ca2+-dependent function of CD8+ lymphocytes such as cytokine/granzyme production and tumor killing. Kv1.3 and KCa3.1 K+ channels stabilize the negative membrane potential of T cells to maintain Ca2+ influx through CRAC channels. We assessed the expression of Kv1.3, KCa3.1 and CRAC in CD8+ cells from ovarian cancer (OC) patients (n = 7). We found that the expression level of Kv1.3 was higher in patients with malignant tumors than in control or benign tumor groups while the KCa3.1 activity was lower in the malignant tumor group as compared to the others. We demonstrated that the Ca2+ response in malignant tumor patients is higher compared to control groups. We propose that altered Kv1.3 and KCa3.1 expression in CD8+ cells in OC could be a reporter and may serve as a biomarker in diagnostics and that increased Ca2+ response through CRAC may contribute to the impaired CD8+ function. LA - English DB - MTMT ER - TY - JOUR AU - Sanches, Karoline AU - Ashwood, Lauren M. AU - Olushola-Siedoks, Abisola Ave-Maria AU - Wai, Dorothy C. C. AU - Rahman, Arfatur AU - Shakeel, Kashmala AU - Naseem, Muhammad Umair AU - Panyi, György AU - Prentis, Peter J. AU - Norton, Raymond S. TI - Structure-function relationships in ShKT domain peptides: ShKT-Ts1 from the sea anemone Telmatactis stephensoni JF - PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS J2 - PROTEINS VL - 92 PY - 2024 IS - 2 SP - 192 EP - 205 PG - 14 SN - 0887-3585 DO - 10.1002/prot.26594 UR - https://m2.mtmt.hu/api/publication/34320587 ID - 34320587 AB - Diverse structural scaffolds have been described in peptides from sea anemones, with the ShKT domain being a common scaffold first identified in ShK toxin from Stichodactyla helianthus. ShK is a potent blocker of voltage-gated potassium channels (K-V 1.x), and an analog, ShK-186 (dalazatide), has completed Phase 1 clinical trials in plaque psoriasis. The ShKT domain has been found in numerous other species, but only a tiny fraction of ShKT domains has been characterized functionally. Despite adopting the canonical ShK fold, some ShKT peptides from sea anemones inhibit K-V 1.x, while others do not. Mutagenesis studies have shown that a Lys-Tyr (KY) dyad plays a key role in K-V 1.x blockade, although a cationic residue followed by a hydrophobic residue may also suffice. Nevertheless, ShKT peptides displaying an ShK-like fold and containing a KY dyad do not necessarily block potassium channels, so additional criteria are needed to determine whether new ShKT peptides might show activity against potassium channels. In this study, we used a combination of NMR and molecular dynamics (MD) simulations to assess the potential activity of a new ShKT peptide. We determined the structure of ShKT-Ts1, from the sea anemone Telmatactis stephensoni, examined its tissue localization, and investigated its activity against a range of ion channels. As ShKT-Ts1 showed no activity against K-V 1.x channels, we used MD simulations to investigate whether solvent exposure of the dyad residues may be informative in rationalizing and potentially predicting the ability of ShKT peptides to block K-V 1.x channels. We show that either a buried dyad that does not become exposed during MD simulations, or a partially exposed dyad that becomes buried during MD simulations, correlates with weak or absent activity against K-V 1.x channels. Therefore, structure determination coupled with MD simulations, may be used to predict whether new sequences belonging to the ShKT family may act as potassium channel blockers. LA - English DB - MTMT ER - TY - JOUR AU - Elnahriry, Khaled A. AU - Wai, Dorothy C.C. AU - Ashwood, Lauren M. AU - Naseem, Muhammad Umair AU - Szántó, Gábor Tibor AU - Guo, Shaodong AU - Panyi, György AU - Prentis, Peter J. AU - Norton, Raymond S. TI - Structural and functional characterisation of Tst2, a novel TRPV1 inhibitory peptide from the Australian sea anemone Telmatactis stephensoni JF - BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS J2 - BBA-PROTEINS PROTEOM VL - 1872 PY - 2024 IS - 1 SN - 1570-9639 DO - 10.1016/j.bbapap.2023.140952 UR - https://m2.mtmt.hu/api/publication/34151641 ID - 34151641 LA - English DB - MTMT ER - TY - JOUR AU - Kerekes, György AU - Bodoki, Levente AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Tajti, Gábor AU - Katkó, Mónika AU - Végh, Edit AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Horváth, Ágnes AU - Soós, B. AU - Szamosi, Szilvia AU - Hascsi, Z. AU - Harangi, Mariann AU - Panyi, György AU - Szűcs, Gabriella AU - Szekanecz, Zoltán TI - AB0237 EFFECTS OF ONE-YEAR TOFACITINIB THERAPY ON ANGIOGENIC BIOMARKERS IN RHEUMATOID ARTHRITIS JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 82 PY - 2023 IS - S1 SP - 1303 EP - 1303 PG - 1 SN - 0003-4967 DO - 10.1136/annrheumdis-2023-eular.2331 UR - https://m2.mtmt.hu/api/publication/34775337 ID - 34775337 LA - English DB - MTMT ER - 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 -