TY - JOUR AU - Szeltner, Zoltán AU - Ferenc, Györgyi AU - Juhász, Tünde AU - Kupihár, Zoltán AU - Váradi, Zoltán AU - Szüts, Dávid AU - Kovács, Lajos TI - Probing telomeric-like G4 structures with full or partial 2′-deoxy-5-hydroxyuridine substitutions JF - BIOCHIMIE J2 - BIOCHIMIE VL - 214 PY - 2023 IS - Part A SP - 33 EP - 44 PG - 12 SN - 0300-9084 DO - 10.1016/j.biochi.2023.01.009 UR - https://m2.mtmt.hu/api/publication/33697937 ID - 33697937 N1 - Institute of Enzymology, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, Budapest, H-1117, Hungary Nucleic Acid Synthesis Laboratory, Biological Research Centre, Eötvös Loránd Research Network, Temesvári Krt. 62, Szeged, H-6726, Hungary Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, Budapest, H-1117, Hungary Department of Medicinal Chemistry, University of Szeged, Dom Tér 8, Szeged, H-6720, Hungary Export Date: 13 March 2023 CODEN: BICMB Correspondence Address: Szüts, D.; Institute of Enzymology, Magyar Tudósok Körútja 2, Hungary; email: szuts.david@ttk.hu Correspondence Address: Kovács, L.; Department of Medicinal Chemistry, Dom Tér 8, Hungary; email: kovacs.lajos@med.u-szeged-hu Funding details: Eötvös Loránd Tudományegyetem, ELTE Funding details: National Research, Development and Innovation Office, 2018–1.2.1-NKP-2018-00005, K128801 Funding text 1: We thank Mihály Kovács and Gábor Harami (ELTE) for supplying us with BLM helicase. This work was supported by the National Research Development and Innovation Office of Hungary (grants no. K128801 and 2018–1.2.1-NKP-2018-00005 ). Funding text 2: We thank Mihály Kovács and Gábor Harami (ELTE) for supplying us with BLM helicase. This work was supported by the National Research Development and Innovation Office of Hungary (grants no. K128801 and 2018–1.2.1-NKP-2018-00005). AB - Guanine quadruplexes (G4s) are stable four-stranded secondary DNA structures held together by noncanonical G-G base tetrads. We synthesised the nucleoside analogue 2′-deoxy-5-hydroxyuridine (H) and inserted its phosphoramidite into telomeric repeat-type model oligonucleotides. Full and partial substitutions were made, replacing all guanines in all the three tetrads of a three-tier G4 structure, or only in the putative upper, central, or lower tetrads. We characterised these modified structures using CD, UV absorbance spectroscopy, native gel studies, and a capture oligo-based G4 disruption kinetic assay. The strand separation activity of BLM helicase on these substituted structures was also investigated. Two of the partially H-substituted constructs adopted G4-like structures, but displayed lower thermal stabilities compared to unsubstituted G4. The construct modified in its central tetrad remained mostly denatured, but the possibility of a special structure for the fully replaced variant remained open. H substitutions did not interfere with the G4-resolving activity of BLM helicase, but its efficiency was highly influenced by construct topology and even more by the G4 ligand PhenDC3. Our results suggest that the H modification can be incorporated into G quadruplexes, but only at certain positions to maintain G4 stability. The destabilizing effect observed for 2′-deoxy-5-hydroxyuridine indicates that the cytosine deamination product 5-hydroxyuracil and its nucleoside counterpart in RNA (5-hydroxyuridine), might also be destabilizing in cellular DNA and RNA quadruplexes. The kinetic assay employed in this study can be generally employed for a fast comparison of the stabilities of various G4s either in their free or ligand-bound states. © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) LA - English DB - MTMT ER - TY - JOUR AU - Kupihár, Zoltán AU - Ferenc, Györgyi AU - Petrovicz, Vencel László AU - Fáy, Viktória R. AU - Kovács, Lajos AU - Martinek, Tamás AU - Hegedüs, Zsófia TI - Improved Metal-Free Approach for the Synthesis of Protected Thiol Containing Thymidine Nucleoside Phosphoramidite and Its Application for the Synthesis of Ligatable Oligonucleotide Conjugates JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 1 PG - 16 SN - 1999-4923 DO - 10.3390/pharmaceutics15010248 UR - https://m2.mtmt.hu/api/publication/33597958 ID - 33597958 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFIH PD 135324, K 128801, K 134754]; Ministry of Innovation and Technology of Hungary through the National Research, Development and Innovation Fund [TKP2021-EGA-32] Funding text: This work received funding from the National Research, Development and Innovation Office of Hungary-NKFIH PD 135324 (Z.H.), K 128801 (L.K.) and K 134754 (T.A.M.). Support by the Ministry of Innovation and Technology of Hungary through the National Research, Development and Innovation Fund (TKP2021-EGA-32) is acknowledged. AB - Oligonucleotide conjugates are versatile scaffolds that can be applied in DNA-based screening platforms and ligand display or as therapeutics. Several different chemical approaches are available for functionalizing oligonucleotides, which are often carried out on the 5′ or 3′ end. Modifying oligonucleotides in the middle of the sequence opens the possibility to ligate the conjugates and create DNA strands bearing multiple different ligands. Our goal was to establish a complete workflow that can be applied for such purposes from monomer synthesis to templated ligation. To achieve this, a monomer is required with an orthogonal functional group that can be incorporated internally into the oligonucleotide sequence. This is followed by conjugation with different molecules and ligation with the help of a complementary template. Here, we show the synthesis and the application of a thiol-modified thymidine nucleoside phosphoramidite to prepare ligatable oligonucleotide conjugates. The conjugations were performed both in solution and on solid phase, resulting in conjugates that can be assembled into multivalent oligonucleotides decorated with tissue-targeting peptides using templated ligation. LA - English DB - MTMT ER - TY - JOUR AU - Váradi, Zoltán AU - Paragi, Gábor AU - Kupihár, Zoltán AU - Kele, Zoltán AU - Kovács, Lajos TI - Synthesis of Heterocycles and Nucleosides Forming Higher—Order Structures JF - CHEMISTRY PROCEEDINGS J2 - CHEM PROC VL - 8 PY - 2022 IS - 1 PG - 6 SN - 2673-4583 DO - 10.3390/ecsoc-25-11705 UR - https://m2.mtmt.hu/api/publication/32818711 ID - 32818711 LA - English DB - MTMT ER - TY - JOUR AU - DeLuca, Michael AU - Sternovsky, Zoltan AU - Armes, Steven P. AU - Fielding, Lee A. AU - Horányi, Mihály AU - Janches, Diego AU - Kupihár, Zoltán AU - Munsat, Tobin AU - Plane, John M. C. TI - Differential Ablation of Organic Coatings From Micrometeoroids Simulated in the Laboratory JF - JOURNAL OF GEOPHYSICAL RESEARCH: PLANETS J2 - J GEOPHYS RES PLANET VL - 127 PY - 2022 IS - 4 PG - 17 SN - 2169-9097 DO - 10.1029/2021JE007168 UR - https://m2.mtmt.hu/api/publication/32787583 ID - 32787583 LA - English DB - MTMT ER - TY - JOUR AU - Ferenc, Györgyi AU - Váradi, Zoltán AU - Kupihár, Zoltán AU - Paragi, Gábor AU - Kovács, Lajos TI - Analytical and structural studies for the investigation of oxidative stress in guanine oligonucleotides JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 14 PG - 27 SN - 1661-6596 DO - 10.3390/ijms21144981 UR - https://m2.mtmt.hu/api/publication/31389117 ID - 31389117 N1 - Funding Agency and Grant Number: NKFI [K128801]; GINOP [GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00036] Funding text: This research was funded by NKFI, grant number K128801, and GINOP, grant numbers GINOP-2.3.2-15-2016-00001 and GINOP-2.3.2-15-2016-00036. LA - English DB - MTMT ER - TY - JOUR AU - Szalay, J. R. AU - Pokorny, P. AU - Sternovsky, Z. AU - Kupihár, Zoltán AU - Poppe, A. R. AU - Horanyi, M. TI - Impact Ejecta and Gardening in the Lunar Polar Regions JF - JOURNAL OF GEOPHYSICAL RESEARCH: PLANETS J2 - J GEOPHYS RES PLANET VL - 124 PY - 2019 IS - 1 SP - 143 EP - 154 PG - 12 SN - 2169-9097 DO - 10.1029/2018JE005756 UR - https://m2.mtmt.hu/api/publication/30623188 ID - 30623188 LA - English DB - MTMT ER - TY - GEN AU - Balázs, Csaba AU - Kupihár, Zoltán AU - Kele, Zoltán AU - Szabó, Zoltán AU - Ferenc, Györgyi AU - Kovács, Lajos TI - Quadruplex forming of oligonucleotides containing 2'-deoxy-5-hydroxyuridine ET - 0 PY - 2018 UR - https://m2.mtmt.hu/api/publication/30427692 ID - 30427692 LA - English DB - MTMT ER - TY - CONF AU - Ferenc, Györgyi AU - Balázs, Csaba AU - Paragi, Gábor AU - Kupihár, Zoltán AU - Kele, Zoltán AU - Szabó, Zoltán AU - Kovács, Lajos TI - Study of the quadruplex-forming properties of 2’-deoxy-5-hydroxyuridine-containing oligonucleotides T2 - Straub-Napok PY - 2018 SP - 22 UR - https://m2.mtmt.hu/api/publication/30426990 ID - 30426990 LA - English DB - MTMT ER - TY - JOUR AU - Mészáros, Mária AU - Porkoláb, Gergő AU - Kiss, Lóránd AU - Pilbat, Ana Maria AU - Kóta, Zoltán AU - Kupihár, Zoltán AU - Kéri, Albert AU - Galbács, Gábor AU - Siklós, László AU - Tóth, András AU - Fülöp, Lívia AU - Czirjákné Csete, Mária AU - Sipos, Áron AU - Hulper, P AU - Sipos, Péter AU - Páli, Tibor AU - Rákhely, Gábor AU - Révész, Piroska AU - Deli, Mária Anna AU - Veszelka, Szilvia TI - Niosomes decorated with dual ligands targeting brain endothelial transporters increase cargo penetration across the blood-brain barrier JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 123 ET - 0 PY - 2018 SP - 228 EP - 240 PG - 13 SN - 0928-0987 DO - 10.1016/j.ejps.2018.07.042 UR - https://m2.mtmt.hu/api/publication/3399566 ID - 3399566 AB - Nanoparticles targeting transporters of the blood-brain barrier (BBB) are promising candidates to increase the brain penetration of biopharmacons. Solute carriers (SLC) are expressed at high levels in brain endothelial cells and show a specific pattern at the BBB. The aim of our study was to test glutathione and ligands of SLC transporters as single or dual BBB targeting molecules for nanovesicles. High mRNA expression levels for hexose and neutral amino acid transporting SLCs were found in isolated rat brain microvessels and our rat primary cell based co-culture BBB model. Niosomes were derivatized with glutathione and SLC ligands glucopyranose and alanine. Serum albumin complexed with Evans blue (67kDa), which has a very low BBB penetration, was selected as a cargo. The presence of targeting ligands on niosomes, especially dual labeling, increased the uptake of the cargo molecule in cultured brain endothelial cells. This cellular uptake was temperature dependent and could be decreased with a metabolic inhibitor and endocytosis blockers filipin and cytochalasin D. Making the negative surface charge of brain endothelial cells more positive with a cationic lipid or digesting the glycocalyx with neuraminidase elevated the uptake of the cargo after treatment with targeted nanocarriers. Treatment with niosomes increased plasma membrane fluidity, suggesting the fusion of nanovesicles with endothelial cell membranes. Targeting ligands elevated the permeability of the cargo across the BBB in the culture model and in mice, and dual-ligand decoration of niosomes was more effective than single ligand labeling. Our data indicate that dual labeling with ligands of multiple SLC transporters can potentially be exploited for BBB targeting of nanoparticles. LA - English DB - MTMT ER - TY - PAT AU - Kupihár, Zoltán AU - Bodnár, Brigitta AU - Kovács, Lajos TI - 5'-linkerrel módosított nukleozidok CY - Country:10001(1) PY - 2017 UR - https://m2.mtmt.hu/api/publication/3327529 ID - 3327529 LA - Hungarian DB - MTMT ER -