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1.

001-es BibID:BIBFORM096063
035-os BibID:(WoS)000655229800001 (Scopus)85106641226
Első szerző:Batta Gyula (biológus)
Cím:Statin-boosted cellular uptake and endosomal escape of penetratin due to reduced membrane dipole potential / Gyula Batta, Levente Karpati, Gabriela Fulaneto Henrique, Gabriella Toth, Szabolcs Tarapcsak, Tamas Kovacs, Florina Zakany, Istvan M. Mandity, Peter Nagy
Dátum:2021
ISSN:0007-1188
Megjegyzések:Background and purpose: Cell penetrating peptides are promising tools for delivery of cargo into cells, but factors limiting or facilitating their cellular uptake are largely unknown. We set out to study the effect of the biophysical properties of the cell membrane on the uptake of penetratin, a cell penetrating peptide. Experimental approach: Using labeling with pH-insensitive and pH-sensitive dyes, the kinetics of cellular uptake and endo-lysosomal escape of penetratin were studied by flow cytometry. Key results: We report that escape of penetratin from acidic endo-lysosomal compartments is retarded compared to its total cellular uptake. The membrane dipole potential, known to alter transmembrane transport of charged molecules, is shown to be negatively correlated with the concentration of penetratin in the cytoplasmic compartment. Treatment of cells with therapeutically relevant concentrations of atorvastatin, an inhibitor of HMG-CoA reductase and cholesterol synthesis, significantly increased endosomal escape of penetratin in two different cell types. This effect of atorvastatin correlated with its ability to decrease the membrane dipole potential. Conclusions and implications: These results highlight the importance of the dipole potential in regulating cellular uptake of cell penetrating peptides and suggest a clinically relevant way of boosting this process.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:British Journal Of Pharmacology. - 178 : 18 (2021), p. 3667-3681. -
További szerzők:Kárpáti Levente (1968-) (okleveles vegyész) Henrique, Gabriela Fulaneto Tóth Gabriella (1996-) (tudományos segédmunkatárs) Tarapcsák Szabolcs (1989-) (Molekuláris biológus) Kovács Tamás (1985-) (általános orvos) Zákány Florina (1989-) (általános orvos) Mándity István M. Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:2018-1.2.1-NKP
Egyéb
GINOP-2.3.2-15-2016-00020
GINOP
GINOP-2.3.2-15-2016-00044
GINOP
K120302
OTKA
ANN133421
Egyéb
Internet cím:Szerző által megadott URL
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2.

001-es BibID:BIBFORM123944
035-os BibID:(scopus)85202905797 (wos)001293277100001
Első szerző:Cs. Szabó Bence (orvos)
Cím:Novel insights into the modulation of the voltage-gated potassium channel KV1.3 activation gating by membrane ceramides / Cs. Szabo Bence, Szabo Mate, Nagy Peter, Varga Zoltan, Panyi Gyorgy, Kovacs Tamas, Zakany Florina
Dátum:2024
ISSN:0022-2275
Megjegyzések:Membrane lipids extensively modulate the activation gating of voltage-gated potassium channels (KV), however, much less is known about the mechanisms of ceramide and glucosylceramide actions including which structural element is the main intramolecular target and whether there is any contribution of indirect, membrane biophysics-related mechanisms to their actions. We used two-electrode voltage-clamp fluorometry capable of recording currents and fluorescence signals to simultaneously monitor movements of the pore domain (PD) and the voltage sensor domain (VSD) of the KV1.3 ion channel after attaching an MTS-TAMRA fluorophore to a cysteine introduced into the extracellular S3-S4 loop of the VSD. We observed rightward shifts in the conductance-voltage (G-V) relationship, slower current activation kinetics, and reduced current amplitudes in response to loading the membrane with C16-ceramide (Cer) or C16-glucosylceramide (GlcCer). When analyzing VSD movements, only Cer induced a rightward shift in the fluorescence signal-voltage (F-V) relationship and slowed fluorescence activation kinetics, whereas GlcCer exerted no such effects. These results point at a distinctive mechanism of action with Cer primarily targeting the VSD, while GlcCer only the PD of KV1.3. Using environment-sensitive probes and fluorescence-based approaches, we show that Cer and GlcCer similarly increase molecular order in the inner, hydrophobic regions of bilayers, however, Cer induces a robust molecular reorganization at the membrane-water interface. We propose that this unique ordering effect in the outermost membrane layer in which the main VSD rearrangement involving an outward sliding of the top of S4 occurs can explain the VSD targeting mechanism of Cer, which is unavailable for GlcCer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
ceramides
glycolipids
fluorescence microscopy
lipids
physical biochemistry
two-electrode voltage-clamp fluorometry
membrane biophysics
ion channels
KV1.3
lipid-protein interactions
Megjelenés:Journal Of Lipid Research. - 65 : 8 (2024), p. 1-17.-
További szerzők:Szabó Máté (1996-) (általános orvos) Nagy Péter (1971-) (biofizikus) Varga Zoltán (1969-) (biofizikus, szakfordító) Panyi György (1966-) (biofizikus) Kovács Tamás (1985-) (általános orvos) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:FK146740
OTKA
FK143400
OTKA
K138075
OTKA
ANN133421
OTKA
K132906
OTKA
K143071
OTKA
ÚNKP-23-4-II-DE-169
Egyéb
ÚNKP-23-5-DE-488
Egyéb
ÚNKP-23-3-II-DE-426
Egyéb
Bolyai János kutatási ösztöndíj BO/00392/23
MTA
Bolyai János kutatási ösztöndíj BO/00676/24
MTA
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM129250
035-os BibID:(scopus)105001325615 (wos)001460543600001
Első szerző:Huntošová, Veronika
Cím:The potential of metal-organic framework MIL-101(Al)-NH2 in the forefront of antiviral protection of cells via interaction with SARS-CoV-2 spike RBD protein and their antibacterial action mediated with hypericin and photodynamic treatment / Huntosová Veronika, Benziane Anass, Zauska Lubos, Ambro Lubos, Olejárová Sona, Joniová Jaroslava, Hlávková Nina, Wagnieres Georges, Zelenková Gabriela, Diko Pavel, Bednarcík Jozef, Zákány Florina, Kovács Tamás, Sedlák Erik, Vámosi György, Almási Miroslav
Dátum:2025
ISSN:0021-9797
Megjegyzések:The global pandemic of SARS-CoV-2 has highlighted the necessity for innovative therapeutic solutions. This research presents a new formulation utilising the metal?organic framework MIL-101(Al)?NH2, which is loaded with hypericin, aimed at addressing viral and bacterial challenges. Hypericin, recognised for its antiviral and antibacterial efficacy, was encapsulated to mitigate its hydrophobicity, improve bioavailability, and utilise its photodynamic characteristics. The MIL-101(Al)?NH2 Hyp complex was synthesised, characterised, and evaluated for its biological applications for the first time. The main objective of this study was to demonstrate the multimodal potential of such a construct, in particular the effect on SARS-CoV-2 protein levels and its interaction with cells. Both in vitro and in vivo experiments demonstrated the effective transport of hypericin to cells that express ACE2 receptors, thereby mimicking mechanisms of viral entry. In addition, hypericin found in the mitochondria showed selective phototoxicity when activated by light, leading to a decrease in the metabolic activity of glioblastoma cells. Importantly, the complex also showed antibacterial efficacy by selectively targeting Gram-positive Staphylococcus epidermidis compared to Gram-negative Escherichia coli under photodynamic therapy (PDT) conditions. To our knowledge, this study was the first to demonstrate the interaction between hypericin, MIL-101(Al)?NH2 and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which inhibits cellular uptake and colocalises with ACE2-expressing cells. Therefore, the dual functionality of the complex ? targeting the viral RBD and the antibacterial effect via PDT ? emphasises its potential to mitigate complications of viral infections, such as secondary bacterial infections. In summary, these results suggest that MIL-101(Al)?NH2 Hyp is a promising multifunctional therapeutic agent for antiviral and antibacterial applications, potentially contributing to the improvement of COVID-19 treatment protocols and the treatment of co-infections.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
MIL-10l(Al)-NH2
Hypericin
ACE2 receptors
RBD spike protein
Photodynamic therapy
Selectivity
Megjelenés:Journal Of Colloid And Interface Science. - 691 (2025), p. 1-18. -
További szerzők:Benziane, Anass (1990-) (molekuláris biológus) Zauška, Ľuboš Ambro, Lubos Olejárová, Sona Joniová, Jaroslava Hlávková, Nina Wagnieres, Georges Zelenková, Gabriela Diko, Pavel Bednarcík, Jozef Zákány Florina (1989-) (általános orvos) Kovács Tamás (1985-) (általános orvos) Sedlák Erik Vámosi György (1967-) (biofizikus) Almáši, Miroslav
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM126309
035-os BibID:(scopus)85213518906 (wos)001387847600001
Első szerző:Kovács Tamás (általános orvos)
Cím:Inhibition of the HV1 voltage-gated proton channel compromises the viability of human polarized macrophages in a polarization- and ceramide-dependent manner / Kovacs Tamas, Cs. Szabo Bence, Kothalawala Rosemary Chandrakanthi, Szekelyhidi Virag, Nagy Peter, Varga Zoltan, Panyi Gyorgy, Zakany Florina
Dátum:2024
ISSN:1664-3224
Megjegyzések:The human voltage-gated proton channel (HV1) provides an efficient proton extrusion pathway from the cytoplasm contributing to the intracellular pH regulation and the oxidative burst. Although its pharmacological inhibition was previously shown to induce cell death in various cell types, no such effects have been examined in polarized macrophages albeit HV1 was suggested to play important roles in these cells. This study highlights that 5-chloro-2- guanidinobenzimidazole (ClGBI), the most widely applied HV1 inhibitor, reduces the viability of human THP-1-derived polarized macrophages at biologically relevant doses with M1 macrophages being the most, and M2 cells the least sensitive to this compound. ClGBI may exert this effect principally by blocking HV1 since the sensitivity of polarized macrophages correlates well with their HV1 expression levels; inhibitors of other macrophage ion channels that may be susceptible for off-target ClGBI effects cause no viability reductions; and Zn2+, another non-specific HV1 blocker, exerts similar effects. As a potential mechanism behind the ClGBI-induced cell death, we identify a complex pH dysregulation involving acidification of the cytoplasm and alkalinization of the lysosomes, which eventually result in membrane ceramide accumulation. Furthermore, ClGBI effects are alleviated by ARC39, a selective acid sphingomyelinase inhibitor supporting the unequivocal significance of ceramide accumulation in the process. Altogether, our results suggest that HV1 inhibition leads to cellular toxicity in polarized macrophages in a polarization-dependent manner, which occurs due to a pH dysregulation and concomitant ceramide overproduction mainly depending on the activity of acid sphingomyelinase. The reduced macrophage viability and plausible concomitant changes in homeostatic M1-M2 balance could contribute to both the therapeutic and potential side effects of HV1 inhibitors that show great promise in the treatment of neuroinflammation and malignant diseases.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
HV1
cell viability
M1 macrophages
polarization
ceramide
pH regulation
acid sphingomyelinase
Megjelenés:Frontiers in Immunology. - 15 (2024), p. 1-18. -
További szerzők:Cs. Szabó Bence (1996-) (orvos) Kothalawala, Rosemary Chandrakanthi Székelyhidi Virág Nagy Péter (1971-) (biofizikus) Varga Zoltán (1969-) (biofizikus, szakfordító) Panyi György (1966-) (biofizikus) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:FK146740,
OTKA
EKÖP-24-4-II-DE-74
Egyéb
FK143400
OTKA
EKÖP-24-2-DE-298
Egyéb
K138075
OTKA
ANN133421
OTKA
K132906
OTKA
K143071
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

5.

001-es BibID:BIBFORM110635
035-os BibID:(WoS)000985072100001 (Scopus)85151447550
Első szerző:Kovács Tamás (általános orvos)
Cím:Veklury (remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content / Kovacs Tamas, Kurtan Kitti, Varga Zoltan, Nagy Peter, Panyi Gyorgy, Zakany Florina
Dátum:2023
ISSN:0007-1188
Megjegyzések: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 cholesteroldepleting 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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
cholesterol
cyclodextrin
remdesivir
SARS-CoV-2
spike glycoprotein
Megjelenés:British Journal Of Pharmacology. - 180 : 16 (2023), p. 2064-2084. -
További szerzők:Kurtán Kitti (2000-) Varga Zoltán (1969-) (biofizikus, szakfordító) Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:ANN133421
OTKA
OTKA FK143400
OTKA
K132906
OTKA
K138075
OTKA
K143071
OTKA
UNKP-21-4-II-DE- 137
Egyéb
UNKP-21-4-II-DE-138
Egyéb
EFOP-3.6.2-16-2017-00006
Egyéb
GINOP-2.3.2-15-2016-00015
Egyéb
UNKP-22-4-II-DE-69
Egyéb
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

6.

001-es BibID:BIBFORM105453
035-os BibID:(WOS)000904144700001 (Scopus)85144901772
Első szerző:Kovács Tamás (általános orvos)
Cím:Cyclodextrins : Only Pharmaceutical Excipients or Full-Fledged Drug Candidates? / Kovacs Tamas, Nagy Peter, Panyi Gyorgy, Szente Lajos, Varga Zoltan, Zakany Florina
Dátum:2022
ISSN:1999-4923
Megjegyzések: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.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Pharmaceutics. - 14 (2022), p. 1-38. -
További szerzők:Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Szente Lajos (1951-) (vegyész) Varga Zoltán (1969-) (biofizikus, szakfordító) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:ANN133421
OTKA
K138075
OTKA
FK143400
OTKA
K143071
OTKA
K132906
OTKA
UNKP?22?4?II?DE?69
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

7.

001-es BibID:BIBFORM100300
035-os BibID:(WoS)000770858500001 (Scopus)85124492778
Első szerző:Kovács Tamás (általános orvos)
Cím:It Takes More than Two to Tango : complex, Hierarchal, and Membrane-Modulated Interactions in the Regulation of Receptor Tyrosine Kinases / Kovacs Tamas, Zakany Florina, Nagy Peter
Dátum:2022
ISSN:2072-6694
Megjegyzések:The search for an understanding of how cell fate and motility are regulated is not a purely scientific undertaking, but it can also lead to rationally designed therapies against cancer. The discovery of tyrosine kinases about half a century ago, the subsequent characterization of certain transmembrane receptors harboring tyrosine kinase activity, and their connection to the development of human cancer ushered in a new age with the hope of finding a treatment for malignant diseases in the foreseeable future. However, painstaking efforts were required to uncover the principles of how these receptors with intrinsic tyrosine kinase activity are regulated. Developments in molecular and structural biology and biophysical approaches paved the way towards better understanding of these pathways. Discoveries in the past twenty years first resulted in the formulation of textbook dogmas, such as dimerization-driven receptor association, which were followed by fine-tuning the model. In this review, the role of molecular interactions taking place during the activation of receptor tyrosine kinases, with special attention to the epidermal growth factor receptor family, will be discussed. The fact that these receptors are anchored in the membrane provides ample opportunities for modulatory lipid?protein interactions that will be considered in detail in the second part of the manuscript. Although qualitative and quantitative alterations in lipids in cancer are not sufficient in their own right to drive the malignant transformation, they both contribute to tumor formation and also provide ways to treat cancer. The review will be concluded with a summary of these medical aspects of lipid?protein interactions.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Cancers. - 14 : 4 (2022), p. 1-31. -
További szerzők:Zákány Florina (1989-) (általános orvos) Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:ANN133421
OTKA
K138075
OTKA
UNKP-21-4-II-DE-137
Egyéb
UNKP-21-4-II-DE-138
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

8.

001-es BibID:BIBFORM097599
Első szerző:Kovács Tamás (általános orvos)
Cím:Cyclodextrins exert a ligand-like current inhibitory effect on the KV1.3 ion channel independent of membrane cholesterol extraction / Tamas Kovacs, Tamas Sohajda, Lajos Szente, Peter Nagy, Gyorgy Panyi, Zoltan Varga, Florina Zakany
Dátum:2021
Megjegyzések:Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming water-soluble complexes with a variety of otherwise poorly soluble molecules including cholesterol and different drugs. Consistently, CDs are widely used in research and clinical practice to deplete cholesterol from cellular membranes or to increase solubility and bioavailability of different pharmaceuticals at local concentrations in the millimolar range. Effects of CDs exerted on cellular functions are generally thought to originate from reductions in cholesterol levels. Potential direct, ligand-like CD effects are largely neglected in spite of several recent studies reporting direct interaction between CDs and proteins including AMP activated protein kinase, ?-amyloid peptides, and ?-synuclein. In this study, by using patch-clamp technique, time-resolved quantitation of cholesterol levels and biophysical parameters and applying cholesterol-extracting and non-cholesterol-extracting CDs at 1 and 5 mM concentrations, we provide evidence for a previously unexplored ligand-like, cholesterol-independent current inhibitory effect of CDs on KV1.3, a prototypical voltage-gated potassium channel with pathophysiological relevance invarious autoimmune and neurodegenerative disorders. Our findings propose that potential direct CD effects on KV channels should be taken into consideration when interpreting functional consequences of CD treatments in both research and clinical practice. Furthermore, current-blocking effects of CDs on KV channels at therapeutically relevant concentrations might contribute to additional beneficial or adverse effects during their therapeutic applications.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
cyclodextrin
ligand-like interaction
membrane lipid order
membrane hydration
membrane fluidity
cholesterol
KV1.3
Megjelenés:Frontiers in Molecular Biosciences. - 8 (2021), p. 1-11. -
További szerzők:Sohajda Tamás Szente Lajos (1951-) (vegyész) Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Varga Zoltán (1969-) (biofizikus, szakfordító) Zákány Florina (1989-) (általános orvos)
Pályázati támogatás:UNKP-19-3-III-DE-92
Egyéb
UNKP-21-4-II-DE-138
Egyéb
UNKP-21-4-II-DE-137
Egyéb
NTP-NFTÖ-20-B-0115
Egyéb
EFOP-3.6.1-16-2016-00022
EFOP
GINOP-2.3.2-15-2016-00044
GINOP
OTKA K132906
OTKA
SNN139532
OTKA
K119417
OTKA
ANN133421
OTKA
2019-2.1.11-TÉT-2019-00059
Egyéb
2020-1.1.2-PIACI-KFI-2020-00092
Egyéb
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM070073
Első szerző:Kovács Tamás (általános orvos)
Cím:The dipole potential correlates with lipid raft markers in the plasma membrane of living cells / Kovács Tamás, Batta Gyula, Zákány Florina, Szöllősi János, Nagy Peter
Dátum:2017
ISSN:0022-2275
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of Lipid Research. - 58 : 8 (2017), p. 1681-1691. -
További szerzők:Batta Gyula (1979-) (biológus) Zákány Florina (1989-) (általános orvos) Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00020
Egyéb
GINOP-2.3.2-15-2016-00044
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM066288
035-os BibID:(WOS)000385927600001 (Scopus)84992409144
Első szerző:Kovács Tamás (általános orvos)
Cím:The Dipole Potential Modifies the Clustering and Ligand Binding Affinity of ErbB Proteins and Their Signaling Efficiency / Tamás Kovács, Gyula Batta, Tímea Hajdu, Ágnes Szabó, Tímea Váradi, Florina Zákány, István Csomós, János Szöllősi, Peter Nagy
Dátum:2016
ISSN:2045-2322
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 6 (2016), p. 35850. -
További szerzők:Batta Gyula (1979-) (biológus) Hajdu Tímea (1991-) (biomérnök) Nagyné Szabó Ágnes Timea (1982-) (vegyész) Váradi Tímea (1982-) (okleveles vegyész) Zákány Florina (1989-) (általános orvos) Csomós István (1983-) (molekuláris biológus) Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
Pályázati támogatás:K103906
OTKA
NK101337
OTKA
GINOP-2.3.2-15-2016-00020
GINOP
TÁMOP-4.2.2.A-11/1/KONV-2012-0025
GINOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

11.

001-es BibID:BIBFORM119122
035-os BibID:(WoS)001176727000001 (Scopus)85186901297
Első szerző:Pethő Zoltán (orvos)
Cím:A synthetic flavonoid derivate in the plasma membrane transforms the voltage-clamp fluorometry signal of CiHv1 / Zoltán Pethő, Dávid Pajtás, Martina Piga, Zsuzsanna Magyar, Florina Zakany, Tamas Kovacs, Nace Zidar, Gyorgy Panyi, Zoltan Varga, Ferenc Papp
Dátum:2024
ISSN:1742-464X
Megjegyzések: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 HV1 (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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
CiHv1
flavonoid derivate
fluorescencequenching
membrane fluidity
voltageclamp fluorometry
Megjelenés:Febs Journal. - 29 : 11 (2024), p. 2354-2371. -
További szerzők:Pajtás Dávid (1987-) (vegyész) Piga Martina Magyar Zsuzsanna (1981-) (orvos) Zákány Florina (1989-) (általános orvos) Kovács Tamás (1985-) (általános orvos) Zidar, Nace Panyi György (1966-) (biofizikus) Varga Zoltán (1969-) (biofizikus, szakfordító) Papp Ferenc (1979-) (biofizikus)
Pályázati támogatás:132906
OTKA
2019-2.1.11-TÉT-2019-00059
Egyéb
BO/00355/21/8 Bolyai
MTA
ÚNKP-22-5-DE-420
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM135779
035-os BibID:(scopus)105010325325 (wos)001539049600001
Első szerző:Piga Martina
Cím:Targeting voltage-gated proton channel HV1 : Optimised 5-phenyl-2-aminoimidazoles with anticancer potential / Piga Martina, Domingos Geraldo Jorge, Feher Adam, Papp Ferenc, Bangera Kavya C., Varga Zoltan, Zakany Florina, Kovacs Tamas, Dernovsek Jaka, Tomasic Tihomir, Zidar Nace
Dátum:2025
ISSN:0223-5234
Megjegyzések:The voltage-gated proton channel (HV1) has been linked to the development of tumours, neuroinflammatory diseases, immune disorders and infertility, making HV1 inhibitors promising candidates for therapeutic development. In this study, we designed and synthesized an optimised series of 5-phenyl-2-aminoimidazole-based HV1 inhibitors, with the most potent compounds exhibiting low micromolar IC50 values. Structural analysis highlighted the importance of an unsubstituted 2-aminoimidazole core and flexible linkers for optimal ligand-channel binding, driven by hydrogen bonding and hydrophobic interactions. Antiproliferative assays showed that the most potent HV1 inhibitors had IC50 values in the low micromolar range, with greater efficacy against THP-1 cells (human monocytic leukaemia), which express HV1 at high levels, compared to MCF-7 cells (human breast cancer) with lower HV1 expression. The type II compounds exhibited superior drug-like properties, including improved solubility, plasma protein binding and permeability compared to previous 5-phenyl-2-aminoimidazole-based HV1 inhibitors, as well as robust metabolic stability. However, selectivity over the KV1.3 and NaV1.5 channels remained limited. This work advances the development of HV1 inhibitors. It provides valuable chemical tools to study the role of HV1 in disease pathogenesis and lays the foundation for new therapeutic strategies targeting HV1-mediated signalling pathways.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Anticancer
HV1
Inhibitor
5-phenyl-2-aminoimidazole
Voltage-gated proton channel
Megjelenés:European Journal Of Medicinal Chemistry. - 297 (2025), p. 1-25. -
További szerzők:Domingos, Geraldo Jorge (1991-) (biológus, biotechnológus) Fehér Ádám (1996-) (orvos, biofizikus) Papp Ferenc (1979-) (biofizikus) Bangera, Kavya C. Varga Zoltán (1969-) (biofizikus, szakfordító) Zákány Florina (1989-) (általános orvos) Kovács Tamás (1985-) (általános orvos) Dernovsek, Jaka Tomasic, Tihomir Zidar, Nace
Pályázati támogatás:K132906
OTKA
FK146740
OTKA
OTKA FK143400
OTKA
ÚNKP-23-3-II-DE-10
Egyéb
PhD Excellence Scholarship from the Count István Tisza Foundation for the University of Debrecen
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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