TY - CONF AU - Csámpai, Antal AU - Bánóczi, Zoltán AU - Vass, Elemér AU - Máté, Eiler-Sulyok AU - Harmat, Veronika TI - 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 T2 - Program and book of abstracts PY - 2024 SP - 12 UR - https://m2.mtmt.hu/api/publication/34836469 ID - 34836469 LA - English DB - MTMT ER - TY - JOUR AU - Farkasinszky, Gergely AU - Péliné Szabó, Judit AU - Károlyi, Péter AU - Rácz, Szilvia AU - Dénes, Noémi AU - Papp, Tamás AU - Király, József AU - Szabó, Zsuzsanna AU - Kertész, István AU - Mező, Gábor AU - Halmos, Gábor AU - Képes, Zita AU - Trencsényi, György TI - In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 16 PY - 2024 IS - 4 SN - 1999-4923 DO - 10.3390/pharmaceutics16040542 UR - https://m2.mtmt.hu/api/publication/34820368 ID - 34820368 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Illien, Françoise AU - Bánóczi, Zoltán AU - Sagan, Sandrine TI - A QUANTITATIVE METHOD TO DISTINGUISH CYTOSOLIC FROM ENDOSOME‐TRAPPED CELL‐PENETRATING PEPTIDES JF - CHEMBIOCHEM J2 - CHEMBIOCHEM PY - 2024 SN - 1439-4227 DO - 10.1002/cbic.202400198 UR - https://m2.mtmt.hu/api/publication/34785967 ID - 34785967 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Tarchoun, Karima AU - Soltész, Dóra AU - Farkas, Viktor AU - Lee, Ho-Jin AU - Szabó, Ildikó AU - Bánóczi, Zoltán TI - Influence of Aza-Glycine Substitution on the Internalization of Penetratin JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 16 PY - 2024 IS - 4 SN - 1999-4923 DO - 10.3390/pharmaceutics16040477 UR - https://m2.mtmt.hu/api/publication/34765015 ID - 34765015 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Béres, Kende Attila AU - Dürvanger, Zsolt AU - Homonnay, Zoltán AU - Nagyné Bereczki, Laura AU - Barta Holló, Berta AU - Farkas, Attila AU - Petruševski, Vladimir M. AU - Kótai, László TI - 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 JF - INORGANICS J2 - INORGANICS VL - 12 PY - 2024 IS - 4 PG - 28 SN - 2304-6740 DO - 10.3390/inorganics12040094 UR - https://m2.mtmt.hu/api/publication/34753165 ID - 34753165 N1 - Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest, H-1117, Hungary György Hevesy PhD School of Chemistry, ELTE Eötvös Loránd University, Budapest, H-1053, Hungary Structural Chemistry and Biology Laboratory, Institute of Chemistry, ELTE Eötvös Loránd University, Budapest, H-1117, Hungary ELKH-ELTE Protein Modelling Research Group, Budapest, H-1117, Hungary Institute of Chemistry, ELTE Eötvös Loránd University, Budapest, H-1053, Hungary Centre for Structural Science, HUN-REN Research Centre for Natural Sciences, Budapest, H-1117, Hungary Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Novi Sad, SRB-21000, Serbia Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Budapest, H-1117, Hungary Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, Skopje, MK-1000, North Macedonia Deuton-X Ltd., Érd, H-2030, Hungary Export Date: 3 May 2024 Correspondence Address: Kótai, L.; Institute of Materials and Environmental Chemistry, Hungary; email: kotai.laszlo@ttk.hu AB - [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. LA - English DB - MTMT ER - TY - PAT AU - Tímár, József AU - Hegedus, Balázs AU - Baranyi, Marcell AU - Molnár, Eszter AU - Tóvári, József AU - Randelovic, Ivan AU - Perczel, András AU - Keseru, György AU - Buday, László TI - Farnesyl-transferase inhibitors and kras inhibitors for treating kras mutant cancers PY - 2024 UR - https://m2.mtmt.hu/api/publication/34720994 ID - 34720994 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Enyedi, Kata Nóra AU - Basa, Bettina AU - Mező, Gábor AU - Lajkó, Eszter TI - Photoinduced Hydrogel-Forming Caged Peptides with Improved Solubility JF - ACS OMEGA J2 - ACS OMEGA VL - 9 PY - 2024 IS - 6 SP - 6894 EP - 6900 PG - 7 SN - 2470-1343 DO - 10.1021/acsomega.3c08289 UR - https://m2.mtmt.hu/api/publication/34546805 ID - 34546805 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Ildikó AU - Biri-Kovács, Beáta AU - Vári, Balázs AU - Randelovic, Ivan AU - Mező, Diána AU - Juhász, Éva AU - Halmos, Gábor AU - Bősze, Szilvia AU - Tóvári, József AU - Mező, Gábor TI - Targeting the Melanocortin 1 Receptor in Melanoma: Biological Activity of α-MSH–Peptide Conjugates JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 2 PG - 21 SN - 1661-6596 DO - 10.3390/ijms25021095 UR - https://m2.mtmt.hu/api/publication/34514820 ID - 34514820 N1 - HUN-REN–ELTE Research Group of Peptide Chemistry, Budapest, 1117, Hungary MTA-TTK “Momentum” Peptide-Based Vaccines Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest, 1117, Hungary National Tumor Biology Laboratory, Department of Experimental Pharmacology, National Institute of Oncology, Budapest, 1122, Hungary School of Ph.D. Studies, Doctoral School of Pathological Sciences, Semmelweis University, Budapest, 1085, Hungary Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Debrecen, 4032, Hungary Institute of Chemistry, Eötvös Loránd University, Budapest, 1117, Hungary Cited By :1 Export Date: 25 April 2024 Correspondence Address: Mező, G.; HUN-REN–ELTE Research Group of Peptide ChemistryHungary; email: gabor.mezo@ttk.elte.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Dembo, António AU - Ferenczi, Etelka AU - Jernei, Tamás AU - Bor, Andrea AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Varga, Szilárd AU - Csámpai, Antal TI - CuAAC-Based Synthesis, Copper-Catalyzed Aldehyde-Forming Hydrolytic Fission and Antiproliferative Evaluation of Novel Ferrocenoylamino-Substituted Triazole-Tethered Quinine–Chalcone Hybrids JF - MOLECULES J2 - MOLECULES VL - 29 PY - 2024 IS - 2 PG - 23 SN - 1420-3049 DO - 10.3390/molecules29020375 UR - https://m2.mtmt.hu/api/publication/34499406 ID - 34499406 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Ferentzi, Kristóf AU - Nagy-Fazekas, Dóra AU - Farkas, Viktor AU - Perczel, András TI - Synthesis of small protein domains by automated flow chemistry JF - REACTION CHEMISTRY & ENGINEERING J2 - REACT CHEM ENG VL - 9 PY - 2023 IS - 1 SP - 58 EP - 69 PG - 12 SN - 2058-9883 DO - 10.1039/D3RE00324H UR - https://m2.mtmt.hu/api/publication/34398184 ID - 34398184 N1 - Hevesy György PhD School of Chemistry, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány. 1/A, Budapest, H-1117, Hungary Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány. 1/A, Budapest, H-1117, Hungary HUN-REN-ELTE Protein Modeling Research Group, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány. 1/A, Budapest, H-1117, Hungary Export Date: 2 April 2024 Correspondence Address: Perczel, A.; Laboratory of Structural Chemistry and Biology, Pázmány Péter sétány. 1/A, Hungary; email: perczel.andras@ttk.elte.hu AB - 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... LA - English DB - MTMT ER -