@CONFERENCE{MTMT:34836469, title = {Enantio- and Diastereoselective synthesis of [3]Ferrocenophanes by Sequential Conjugate Addition of Nitromethane and Malonitrile to 1,1’- Diformylferrocene-derived bis Chalcones Using Bifunctional Chinchona based Organocatalys}, url = {https://m2.mtmt.hu/api/publication/34836469}, author = {Csámpai, Antal and Bánóczi, Zoltán and Vass, Elemér and Máté, Eiler-Sulyok and Harmat, Veronika}, booktitle = {Program and book of abstracts}, unique-id = {34836469}, year = {2024}, pages = {12}, orcid-numbers = {Csámpai, Antal/0000-0003-2107-7309; Bánóczi, Zoltán/0000-0003-1880-4042; Vass, Elemér/0000-0001-8898-3846; Harmat, Veronika/0000-0002-1866-9904} } @article{MTMT:34820368, title = {In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study}, url = {https://m2.mtmt.hu/api/publication/34820368}, author = {Farkasinszky, Gergely and Péliné Szabó, Judit and Károlyi, Péter and Rácz, Szilvia and Dénes, Noémi and Papp, Tamás and Király, József and Szabó, Zsuzsanna and Kertész, István and Mező, Gábor and Halmos, Gábor and Képes, Zita and Trencsényi, György}, doi = {10.3390/pharmaceutics16040542}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {16}, unique-id = {34820368}, issn = {1999-4923}, abstract = {Background: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD). Methods: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[18F]FDG and [68Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts. Results: Due to a cellular adaptation to hypoxia, a gradual increase in [68Ga]Ga-NOTA-c(NGR) and 2-[18F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups. Conclusions: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD.}, year = {2024}, eissn = {1999-4923}, orcid-numbers = {Mező, Gábor/0000-0002-7618-7954; Képes, Zita/0000-0003-2889-8521; Trencsényi, György/0000-0001-6456-6212} } @article{MTMT:34785967, title = {A QUANTITATIVE METHOD TO DISTINGUISH CYTOSOLIC FROM ENDOSOME‐TRAPPED CELL‐PENETRATING PEPTIDES}, url = {https://m2.mtmt.hu/api/publication/34785967}, author = {Illien, Françoise and Bánóczi, Zoltán and Sagan, Sandrine}, doi = {10.1002/cbic.202400198}, journal-iso = {CHEMBIOCHEM}, journal = {CHEMBIOCHEM}, unique-id = {34785967}, issn = {1439-4227}, abstract = {Cell‐penetrating peptides are known to penetrate cells through endocytosis and translocation. The two pathways are hardly distinguished in current cell assays. We developed a reliable, simple and robust method to distinguish and quantify independently the two routes. The assay requires (DABCYL) 4‐(dimethylaminoazo)benzene‐4‐carboxylic acid‐ and (CF) carboxyfluorescein‐labeled peptides. When the labeled peptide is intact, the fluorescence signal is weak thanks to the dark quenching property of DABCYL. A 10‐fold higher fluorescence signal is measured when the labeled peptide is degraded. By referring to a standard fluorescent curve according to the concentration of the hydrolyzed peptide, we have access to the internalized peptide quantity. Therefore, cell lysis after internalization permits to determine the total quantity of intracellular peptide. The molecular state of the internalized peptide (intact or degraded), depends on its location in cells (cytosol vs endo‐lysosomes), and can be blocked by boiling cells. This boiling step results indeed in denaturation and inhibition of the cellular enzymes. The advantage of this method is the possibility to quantify translocation at 37°C and to compare it to the 4°C condition, where all endocytosis processes are inhibited. We found that ranking of the translocation efficacy is DABCYL‐R6‐(εCF)K >> DABCYL‐R4‐(εCF)K ≥ CF‐R9.}, year = {2024}, eissn = {1439-7633}, orcid-numbers = {Bánóczi, Zoltán/0000-0003-1880-4042} } @article{MTMT:34765015, title = {Influence of Aza-Glycine Substitution on the Internalization of Penetratin}, url = {https://m2.mtmt.hu/api/publication/34765015}, author = {Tarchoun, Karima and Soltész, Dóra and Farkas, Viktor and Lee, Ho-Jin and Szabó, Ildikó and Bánóczi, Zoltán}, doi = {10.3390/pharmaceutics16040477}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {16}, unique-id = {34765015}, issn = {1999-4923}, abstract = {The cell-penetrating peptide (CPP) penetratin has gained much attention over many years due to its potential role as a transporter for a broad range of cargo into cells. The modification of penetratin has been extensively investigated too. Aza-peptides are peptide analogs in which one or more of the amino residues are replaced by a semicarbazide. This substitution results in conformational restrictions and modifications in hydrogen bonding properties, which affect the structure and may lead to enhanced activity and selectivity of the modified peptide. In this work, the Trp residues of penetratin were substituted by aza-glycine or glycine residues to examine the effect of these modifications on the cellular uptake and the internalization mechanism. The substitution of Trp48 or Trp48,56 dramatically reduced the internalization, showing the importance of Trp48 in cellular uptake. Interestingly, while aza-glycine in the position of Trp56 increased the cellular uptake, Gly reduced it. The two Trp-modified derivatives showed altered internalization pathways, too. Based on our knowledge, this is the first study about the effect of aza-amino acid substitution on the cell entry of CPPs. Our results suggest that aza-amino acid insertion is a useful modification to change the internalization of a CPP.}, year = {2024}, eissn = {1999-4923}, orcid-numbers = {Farkas, Viktor/0000-0002-8815-2783; Lee, Ho-Jin/0000-0002-3251-4984; Szabó, Ildikó/0000-0002-9844-7841; Bánóczi, Zoltán/0000-0003-1880-4042} } @article{MTMT:34753165, title = {Insight into the Structure and Redox Chemistry of [Carbonatotetraamminecobalt(III)] Permanganate and Its Monohydrate as Co-Mn-Oxide Catalyst Precursors of the Fischer-Tropsch Synthesis}, url = {https://m2.mtmt.hu/api/publication/34753165}, author = {Béres, Kende Attila and Dürvanger, Zsolt and Homonnay, Zoltán and Nagyné Bereczki, Laura and Barta Holló, Berta and Farkas, Attila and Petruševski, Vladimir M. and Kótai, László}, doi = {10.3390/inorganics12040094}, journal-iso = {INORGANICS}, journal = {INORGANICS}, volume = {12}, unique-id = {34753165}, abstract = {[Carbonatotetraamminecobalt(III)] permanganate monohydrate was synthesized first in the metathesis reaction of [Co(NH3)4CO3]NO3 and NaMnO4 in aqueous solution. Its thermal dehydration at 100 °C resulted in phase-pure [Co(NH3)4CO3]MnO4 (compound 1). Compounds 1 and 2 (i.e., the hydrated form) were studied with IR, far-IR, and low-temperature Raman spectroscopies, and their vibrational modes were assigned. The lattice parameters were determined by powder X-ray diffraction (PXRD) and single crystal X-ray diffraction (SXRD) methods for the triclinic and orthorhombic compounds 1 and 2, respectively. The detailed structure of compound 2 was determined, and the role of hydrogen bonds in the structural motifs was clarified. UV studies on compounds 1 and 2 showed the distortion of the octahedral geometry of the complex cation during dehydration because of the partial loss of the hydrogen bonds between the crystal water and the ligands of the complex cation. The thermal decomposition consists of a solid phase quasi-intramolecular redox reaction between the ammonia ligands and permanganate anions with the formation of ammonia oxidation products (H2O, NO, N2O, and CO2). The solid phase reaction product is amorphous cobalt manganese oxide containing ammonium, carbonate (and nitrate) anions. The temperature-controlled thermal decomposition of compound 2 in toluene at 110 °C showed that one of the decomposition intermediates is ammonium nitrate. The decomposition intermediates are transformed into Co1.5Mn1.5O4 spinel with MnCo2O4 structure upon further heating. Solid compound 2 gave the spinel at 500 °C both in an inert and air atmosphere, whereas the sample pre-treated in toluene at 110 °C without and with the removal of ammonium nitrate by aqueous washing, gave the spinel already at 300 and 400 °C, respectively. The molten NH4NO3 is a medium to start spinel crystallization, but its decomposition stops further crystal growth of the spinel phase. By this procedure, the particle size of the spinel product as low as ~4.0 nm could be achieved for the treatments at 300 and 400 °C, and it increased only to 5.7 nm at 500 °C. The nano-sized mixed cobalt manganese oxides are potential candidates as Fischer-Tropsch catalysts.}, year = {2024}, eissn = {2304-6740}, orcid-numbers = {Béres, Kende Attila/0000-0003-4257-0581; Dürvanger, Zsolt/0000-0002-2652-4916; Homonnay, Zoltán/0000-0001-5299-5394; Barta Holló, Berta/0000-0002-5786-442X; Farkas, Attila/0000-0002-8877-2587} } @book{MTMT:34720994, title = {Farnesyl-transferase inhibitors and kras inhibitors for treating kras mutant cancers}, url = {https://m2.mtmt.hu/api/publication/34720994}, author = {Tímár, József and Hegedus, Balázs and Baranyi, Marcell and Molnár, Eszter and Tóvári, József and Randelovic, Ivan and Perczel, András and Keseru, György and Buday, László}, unique-id = {34720994}, abstract = {The invention relates to cancer biology, more specifically to the treatment of KRAS mutant cancers. A potent cancer therapy is provided by the combination of a farnesyl transferase inhibitor compound and a KRAS inhibitor compound.}, year = {2024}, orcid-numbers = {Perczel, András/0000-0003-1252-6416} } @article{MTMT:34546805, title = {Photoinduced Hydrogel-Forming Caged Peptides with Improved Solubility}, url = {https://m2.mtmt.hu/api/publication/34546805}, author = {Enyedi, Kata Nóra and Basa, Bettina and Mező, Gábor and Lajkó, Eszter}, doi = {10.1021/acsomega.3c08289}, journal-iso = {ACS OMEGA}, journal = {ACS OMEGA}, volume = {9}, unique-id = {34546805}, issn = {2470-1343}, year = {2024}, eissn = {2470-1343}, pages = {6894-6900}, orcid-numbers = {Enyedi, Kata Nóra/0000-0003-3724-5936; Mező, Gábor/0000-0002-7618-7954; Lajkó, Eszter/0000-0002-4796-4646} } @article{MTMT:34514820, title = {Targeting the Melanocortin 1 Receptor in Melanoma: Biological Activity of α-MSH–Peptide Conjugates}, url = {https://m2.mtmt.hu/api/publication/34514820}, author = {Szabó, Ildikó and Biri-Kovács, Beáta and Vári, Balázs and Randelovic, Ivan and Mező, Diána and Juhász, Éva and Halmos, Gábor and Bősze, Szilvia and Tóvári, József and Mező, Gábor}, doi = {10.3390/ijms25021095}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34514820}, issn = {1661-6596}, abstract = {Malignant melanoma is one of the most aggressive and resistant tumor types, with high metastatic properties. Because of the lack of suitable chemotherapeutic agents for treatment, the 5-year survival rate of melanoma patients with regional and distant metastases is lower than 10%. Targeted tumor therapy that provides several promising results might be a good option for the treatment of malignant melanomas. Our goal was to develop novel melanoma-specific peptide–drug conjugates for targeted tumor therapy. Melanocortin-1-receptor (MC1R) is a cell surface receptor responsible for melanogenesis and it is overexpressed on the surface of melanoma cells, providing a good target. Its native ligand, α-MSH (α-melanocyte-stimulating hormone) peptide, or its derivatives, might be potential homing devices for this purpose. Therefore, we prepared three α-MSH derivative–daunomycin (Dau) conjugates and their in vitro and in vivo antitumor activities were compared. Dau has an autofluorescence property; therefore, it is suitable for preparing conjugates for in vitro (e.g., cellular uptake) and in vivo experiments. Dau was attached to the peptides via a non-cleavable oxime linkage that was applied efficiently in our previous experiments, resulting in conjugates with high tumor growth inhibition activity. The results indicated that the most promising conjugate was the compound in which Dau was connected to the side chain of Lys (Ac-SYSNleEHFRWGK(Dau=Aoa)PV-NH2). The highest cellular uptake by melanoma cells was demonstrated using the compound, with the highest tumor growth inhibition detected both on mouse (38.6% on B16) and human uveal melanoma (55% on OMC-1) cells. The effect of the compound was more pronounced than that of the free drug.}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Szabó, Ildikó/0000-0002-9844-7841; Biri-Kovács, Beáta/0000-0001-5803-9969; Vári, Balázs/0000-0001-9919-1502; Randelovic, Ivan/0000-0003-0161-0022; Tóvári, József/0000-0002-5543-3204; Mező, Gábor/0000-0002-7618-7954} } @article{MTMT:34499406, title = {CuAAC-Based Synthesis, Copper-Catalyzed Aldehyde-Forming Hydrolytic Fission and Antiproliferative Evaluation of Novel Ferrocenoylamino-Substituted Triazole-Tethered Quinine–Chalcone Hybrids}, url = {https://m2.mtmt.hu/api/publication/34499406}, author = {Dembo, António and Ferenczi, Etelka and Jernei, Tamás and Bor, Andrea and Schelz, Zsuzsanna and Zupkó, István and Varga, Szilárd and Csámpai, Antal}, doi = {10.3390/molecules29020375}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {29}, unique-id = {34499406}, issn = {1420-3049}, abstract = {A series of novel triazole-tethered ferrocenoylamino-substituted cinchona–chalcone hybrids along with two representative benzoylamino-substituted reference compounds were prepared by three methods of CuAAC chemistry. In line with the limited success or complete failure of attempted conversions with low catalyst loadings, by means of DFT modeling studies, we demonstrated that a substantial part of the Cu(I) ions can be chelated and thus trapped in the aroylamino-substituted cinchona fragment and all of the accessible coordinating sites of the chalcone residues. Accordingly, increased amounts of catalysts were used to achieve acceptable yields; however, the cycloadditions with para-azidochalcones were accompanied by partial or complete aldehyde-forming hydrolytic fission of the enone C=C bond in a substituent-, solvent- and copper load-dependent manner. The experienced hydrolytic stability of the hybrids obtained by cycloadditions with ortho-azidochalcones was interpreted in terms of relative energetics, DFT reactivity indices and MO analysis of simplified models of two isomer copper–enone complexes. The novel hybrids were evaluated on HeLa, MDA-MB-231 and A2780 cell lines and showed substantial activity at low-to-submicromolar concentrations. An organometallic model carrying 3,4,5-trimethoxyphenyl residue in the enone part with a para-disubstituted benzene ring in the central skeletal region was identified as the most potent antiproliferative lead, characterized by submicromolar IC50 values measured on the three investigated cells. The biological assays also disclosed that this ferrocenoylamino-containing lead compound displays a ca. two- to five-fold more substantial antiproliferative effect than its benzoylamino-substituted counterpart.}, year = {2024}, eissn = {1420-3049}, orcid-numbers = {Schelz, Zsuzsanna/0000-0002-8519-4830; Zupkó, István/0000-0003-3243-5300; Varga, Szilárd/0000-0001-9611-5168; Csámpai, Antal/0000-0003-2107-7309} } @article{MTMT:34398184, title = {Synthesis of small protein domains by automated flow chemistry}, url = {https://m2.mtmt.hu/api/publication/34398184}, author = {Ferentzi, Kristóf and Nagy-Fazekas, Dóra and Farkas, Viktor and Perczel, András}, doi = {10.1039/D3RE00324H}, journal-iso = {REACT CHEM ENG}, journal = {REACTION CHEMISTRY & ENGINEERING}, volume = {9}, unique-id = {34398184}, issn = {2058-9883}, abstract = {The most fundamental topological units of proteins are their autonomously folded domains. The rapid and reliable chemical synthesis of domains in the range of 5-10 kDa in size, remains a...}, year = {2023}, eissn = {2058-9883}, pages = {58-69}, orcid-numbers = {Farkas, Viktor/0000-0002-8815-2783; Perczel, András/0000-0003-1252-6416} }