TY - JOUR AU - Hőgye, Fanni AU - Farkas, László Bence AU - Balogh, Álex Kálmán AU - Szilágyi, László AU - Alnukari, Samar AU - Bajza, István AU - Borbás, Anikó AU - Fehér, Krisztina AU - Tóthné Illyés, Tünde Zita AU - Timári, István TI - Saturation Transfer Difference NMR and Molecular Docking Interaction Study of Aralkyl-Thiodigalactosides as Potential Inhibitors of the Human-Galectin-3 Protein JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 3 PG - 18 SN - 1661-6596 DO - 10.3390/ijms25031742 UR - https://m2.mtmt.hu/api/publication/34567562 ID - 34567562 AB - Human Galectin-3 (hGal-3) is a protein that selectively binds to β-galactosides and holds diverse roles in both normal and pathological circumstances. Therefore, targeting hGal-3 has become a vibrant area of research in the pharmaceutical chemistry. As a step towards the development of novel hGal-3 inhibitors, we synthesized and investigated derivatives of thiodigalactoside (TDG) modified with different aromatic substituents. Specifically, we describe a high-yielding synthetic route of thiodigalactoside (TDG); an optimized procedure for the synthesis of the novel 3,3′-di-O-(quinoline-2-yl)methyl)-TDG and three other known, symmetric 3,3′-di-O-TDG derivatives ((naphthalene-2yl)methyl, benzyl, (7-methoxy-2H-1-benzopyran-2-on-4-yl)methyl). In the present study, using competition Saturation Transfer Difference (STD) NMR spectroscopy, we determined the dissociation constant (Kd) of the former three TDG derivatives produced to characterize the strength of the interaction with the target protein (hGal-3). Based on the Kd values determined, the (naphthalen-2-yl)methyl, the (quinolin-2-yl)methyl and the benzyl derivatives bind to hGal-3 94, 30 and 24 times more strongly than TDG. Then, we studied the binding modes of the derivatives in silico by molecular docking calculations. Docking poses similar to the canonical binding modes of well-known hGal-3 inhibitors have been found. However, additional binding forces, cation–π interactions between the arginine residues in the binding pocket of the protein and the aromatic groups of the ligands, have been established as significant features. Our results offer a molecular-level understanding of the varying affinities observed among the synthesized thiodigalactoside derivatives, which can be a key aspect in the future development of more effective ligands of hGal-3. LA - English DB - MTMT ER - TY - GEN AU - Máté, BENEDEK AU - Nagy, Tibor AU - Róth, Gergő AU - Kuki, Ákos AU - Timári, István AU - Zsuga, Miklós AU - Kéki, Sándor TI - Characterization of copolymers using gel permeation chromatography and neural networks, Young Researchers' International Conference on Chemistry and Chemical Engineering PY - 2023 UR - https://m2.mtmt.hu/api/publication/34159529 ID - 34159529 LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Tibor AU - Róth, Gergő AU - Benedek, Máté AU - Kuki, Ákos AU - Timári, István AU - Zsuga, Miklós AU - Kéki, Sándor TI - Enhanced Copolymer Characterization for Polyethers Using Gel Permeation Chromatography Combined with Artificial Neural Networks JF - ANALYTICAL CHEMISTRY J2 - ANAL CHEM VL - 95 PY - 2023 IS - 28 SP - 10504 EP - 10511 PG - 7 SN - 0003-2700 DO - 10.1021/acs.analchem.2c02913 UR - https://m2.mtmt.hu/api/publication/34110916 ID - 34110916 AB - Gel permeation chromatography (GPC) is a generally applied method for the mass analysis of various polymers and copolymers, but it inherently fails to provide additional important information such as the composition of copolymers. However, we will show that GPC measurements using different solvents can yield not just the correct molecular weight but the composition of the copolymer. Accordingly, artificial neural networks (ANNs) have been developed to process the data of GPC measurements and determine the molecular weight and the chemical composition of the copolymers. The target values of the ANNs were obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nuclear magnetic resonance (NMR) spectroscopy. Our GPC-ANN method is demonstrated by the analysis of various poloxamers, i.e., poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO) block copolymers. Two ANNs were constructed. The first one (ANN_1) works in a wider mass range (from 900 to 12,500 dalton), while the second one (ANN_2) produces more output values. ANN_2 can thus predict seven characteristic copolymer parameters, namely, two average molecular weights, the average weight fraction of the EO unit, and four average numbers of the repeat units. The correlation between the experimentally obtained outputs and the predicted ones is high (r > 0.98). The accuracy of the ANNs is very convincing, and both ANNs predict the number-average molecular weight (M-n) with an accuracy below 5%. Furthermore, this work is the first step for creating an open database and applications extending the use of the GPC-ANN method for the analysis of copolymers. LA - English DB - MTMT ER - TY - JOUR AU - Kónya, Zoltán AU - Tamás, István AU - Bécsi, Bálint AU - Lontay, Beáta AU - Hadháziné Raics, Mária AU - Timári, István AU - E Kövér, Katalin AU - Erdődi, Ferenc TI - Phosphorylated Peptide Derived from the Myosin Phosphatase Target Subunit Is a Novel Inhibitor of Protein Phosphatase-1 JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 5 PG - 17 SN - 1661-6596 DO - 10.3390/ijms24054789 UR - https://m2.mtmt.hu/api/publication/33699950 ID - 33699950 AB - Identification of specific protein phosphatase-1 (PP1) inhibitors is of special importance regarding the study of its cellular functions and may have therapeutic values in diseases coupled to signaling processes. In this study, we prove that a phosphorylated peptide of the inhibitory region of myosin phosphatase (MP) target subunit (MYPT1), R690QSRRS(pT696)QGVTL701 (P-Thr696-MYPT1690−701), interacts with and inhibits the PP1 catalytic subunit (PP1c, IC50 = 3.84 µM) and the MP holoenzyme (Flag-MYPT1-PP1c, IC50 = 3.84 µM). Saturation transfer difference NMR measurements established binding of hydrophobic and basic regions of P-Thr696-MYPT1690−701 to PP1c, suggesting interactions with the hydrophobic and acidic substrate binding grooves. P-Thr696-MYPT1690−701 was dephosphorylated by PP1c slowly (t1/2 = 81.6–87.9 min), which was further impeded (t1/2 = 103 min) in the presence of the phosphorylated 20 kDa myosin light chain (P-MLC20). In contrast, P-Thr696-MYPT1690−701 (10–500 µM) slowed down the dephosphorylation of P-MLC20 (t1/2 = 1.69 min) significantly (t1/2 = 2.49–10.06 min). These data are compatible with an unfair competition mechanism between the inhibitory phosphopeptide and the phosphosubstrate. Docking simulations of the PP1c-P-MYPT1690−701 complexes with phosphothreonine (PP1c-P-Thr696-MYPT1690−701) or phosphoserine (PP1c-P-Ser696-MYPT1690−701) suggested their distinct poses on the surface of PP1c. In addition, the arrangements and distances of the surrounding coordinating residues of PP1c around the phosphothreonine or phosphoserine at the active site were distinct, which may account for their different hydrolysis rate. It is presumed that P-Thr696-MYPT1690−701 binds tightly at the active center but the phosphoester hydrolysis is less preferable compared to P-Ser696-MYPT1690−701 or phosphoserine substrates. Moreover, the inhibitory phosphopeptide may serve as a template to synthesize cell permeable PP1-specific peptide inhibitors. LA - English DB - MTMT ER - TY - CHAP AU - Szakács, Bence AU - Kaszás, Tímea AU - Juhászné Tóth, Éva AU - Cservenyák, Ivett AU - Kovács, Tamara AU - Timári, István AU - Juhász, László AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta ED - Mihály, Herczeg TI - Catalyst-free coupling reactions of anhydro-aldose tosylhydrazones with 1H-1,2,3-triazoles and 5-benzyl-2H-tetrazoles: synthesis of C-(β-D-glycopyranosyl)methyl-triazoles and -tetrazoles T2 - Debrecen Colloquium on Carbohydrates 2020 in 2022: Rezső Bognár Memorial Conference on Glycomimetics PB - University of Debrecen CY - Debrecen SN - 9789634904601 PY - 2022 SP - 43. oldal, OL-9 UR - https://m2.mtmt.hu/api/publication/34413868 ID - 34413868 LA - English DB - MTMT ER - TY - BOOK AU - Kaszás, Tímea AU - Szakács, Bence AU - Juhászné Tóth, Éva AU - Cservenyák, Ivett AU - Kovács, Tamara AU - Timári, István AU - Nilsson, Ulf J. AU - Juhász, László AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - Catalyst-free coupling reactions of anhydro-aldose and aromatic tosylhydrazones with tetrazoles and triazoles PY - 2022 UR - https://m2.mtmt.hu/api/publication/34413789 ID - 34413789 N1 - Online, 269. oldal LA - English DB - MTMT ER - TY - BOOK AU - Kaszás, Tímea AU - Szakács, Bence AU - Juhászné Tóth, Éva AU - Cservenyák, Ivett AU - Kovács, Tamara AU - Timári, István AU - Juhász, László AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - Catalyst-free coupling reactions for the synthesis of C-(β-D-glycopyranosyl)methyl-triazoles, -tetrazoles and alkyl/aryl substituted tetrazoles PY - 2022 UR - https://m2.mtmt.hu/api/publication/34413585 ID - 34413585 N1 - Poster, P36 LA - English DB - MTMT ER - TY - CHAP AU - Szakács, Bence AU - Juhászné Tóth, Éva AU - Cservenyák, Ivett AU - Kaszás, Tímea AU - Timári, István AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - N-Tozilhidrazonok fémmentes kapcsolása 1,2,3-triazolokkal T2 - Vegyészkonferencia 2022 PB - Magyar Kémikusok Egyesülete (MKE) CY - Budapest SN - 9786156018113 PY - 2022 SP - 65. oldal, O-39 UR - https://m2.mtmt.hu/api/publication/34413543 ID - 34413543 N1 - Előadás LA - Hungarian DB - MTMT ER - TY - BOOK AU - Szakács, Bence AU - Kaszás, Tímea AU - Cservenyák, Ivett AU - Juhászné Tóth, Éva AU - Timári, István AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - Anhidro-aldóz tozilhidrazonok kapcsolási reakciói 4-aril-1H-1,2,3-triazolokkal PY - 2022 UR - https://m2.mtmt.hu/api/publication/34413487 ID - 34413487 N1 - ISBN 978-963-421-874-6 Előadás LA - Hungarian DB - MTMT ER - TY - GEN AU - Róth, Gergő AU - Nagy, Tibor AU - Kuki, Ákos AU - Hashimov, Mahir AU - Zsófia, Vonza AU - Timári, István AU - Zsuga, Miklós AU - Kéki, Sándor TI - The Polydispersity Ratio and its Implementation for the Interpretation of Pluronics, XXIV. International Mass Spectrometry Conference. Maastricht TS - Maastricht PY - 2022 UR - https://m2.mtmt.hu/api/publication/34160640 ID - 34160640 LA - English DB - MTMT ER -