TY - JOUR AU - Dibello, Estefanía AU - Oddone, Natalia AU - Franco, Jaime AU - Tóthné Illyés, Tünde Zita AU - Medeiros, Andrea AU - Kiss, Attila AU - Hőgye, Fanni AU - E Kövér, Katalin AU - Szilágyi, László AU - Comini, Marcelo A. TI - Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity JF - INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE J2 - INT J PARASITOL-DRUG VL - 24 PY - 2024 PG - 6 SN - 2211-3207 DO - 10.1016/j.ijpddr.2024.100529 UR - https://m2.mtmt.hu/api/publication/34743720 ID - 34743720 AB - Earlier evidences showed that diglycosyl diselenides are active against the infective stage of African trypanosomes (top hits IC50 0.5 and 1.5 μM) but poorly selective (selectivity index <10). Here we extended the study to 33 new seleno-glycoconjugates with the aim to improve potency and selectivity. Three selenoglycosides and three glycosyl selenenylsulfides displayed IC50 against bloodstream Trypanosoma brucei in the sub-μM range (IC50 0.35–0.77 μM) and four of them showed an improved selectivity (selectivity index >38-folds vs. murine and human macrohages). For the glycosyl selenylsulfides, the anti-trypanosomal activity was not significantly influenced by the nature of the moiety attached to the sulfur atom. Except for a quinoline-, and to a minor extent a nitro-derivative, the most selective hits induced a rapid (within 60 min) and marked perturbation of the LMWTredox homeostasis. The formation of selenenylsulfide glycoconjugates with free thiols has been identified as a potential mechanism involved in this process. LA - English DB - MTMT ER - 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 - JOUR AU - Tóthné Illyés, Tünde Zita AU - Malinovská, Lenka AU - Rőth, Erzsébet AU - Tóth, Boglárka AU - Farkas, László Bence AU - Korsák, Marek AU - Wimmerová, Michaela AU - E Kövér, Katalin AU - Csávás, Magdolna TI - Synthesis of Tetravalent Thio- and Selenogalactoside-Presenting Galactoclusters and Their Interactions with Bacterial Lectin PA-IL from Pseudomonas aeruginosa JF - MOLECULES J2 - MOLECULES VL - 26 PY - 2021 IS - 3 PG - 11 SN - 1420-3049 DO - 10.3390/molecules26030542 UR - https://m2.mtmt.hu/api/publication/31845447 ID - 31845447 N1 - Funding Agency and Grant Number: National Research and Development and Innovation Office of Hungary [K119509, K128368]; European Regional Development FundEuropean Commission [GINOP-2.3.2-15-2016-00008]; Janos Bolyai Fellowship of the Hungarian Academy of Sciences; Czech Science FoundationGrant Agency of the Czech Republic [18-18964S]; CIISB research infrastructure - MEYS CR [LM2018127] Funding text: The synthetic work was supported by the National Research and Development and Innovation Office of Hungary (K119509, M.C., K128368, K.E.K.) and co-financed by the European Regional Development Fund under the project GINOP-2.3.2-15-2016-00008. The project was supported by the Janos Bolyai Fellowship (M.C.) of the Hungarian Academy of Sciences. The project was further supported by the Czech Science Foundation (18-18964S). We acknowledge the Biomolecular Interactions and Crystallization Core Facility of CEITEC MU supported by the CIISB research infrastructure (LM2018127 funded by MEYS CR) for their support with obtaining the scientific data presented in this paper. AB - Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-β-d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis. LA - English DB - MTMT ER - TY - JOUR AU - Ferenczi, Renata Kertine AU - Tóthné Illyés, Tünde Zita AU - Király, Sándor Balázs AU - Hoffka, Gyula AU - Szilágyi, László AU - Mándi, Attila AU - Antus, Sándor AU - Kurtán, Tibor TI - Evaluation of Different Synthetic Routes to (2R,3R)-3-Hydroxymethyl-2-(4-hydroxy-3-methoxyphenyl)-1,4-Benzodioxane-6 -Carbaldehyde JF - CURRENT ORGANIC CHEMISTRY J2 - CURR ORG CHEM VL - 23 PY - 2019 IS - 26 SP - 2960 EP - 2968 PG - 9 SN - 1385-2728 DO - 10.2174/1385272823666191212113407 UR - https://m2.mtmt.hu/api/publication/31149376 ID - 31149376 N1 - Funding Agency and Grant Number: National Research Development and Innovation Office [K-112951, K-120181, NN128368]; EUEuropean Union (EU); European Regional Development FundEuropean Union (EU) [GINOP-2.3.2-15-2016-00008, GINOP-2.3.3-15-2016-00004]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences Funding text: Financial support from the National Research Development and Innovation Office (Grant numbers: K-112951, K-120181 and NN128368) is gratefully acknowledged as well as the research was supported by the EU and co-financed by the European Regional Development Fund under the project GINOP-2.3.2-15-2016-00008 and GINOP-2.3.3-15-2016-00004. A. M. thank the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences for financial support. AB - The reported enantioselective synthesis for the preparation of (+)-(2R,3R)-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-1,4-benzodioxane-6-carbaldehyde, precursor for the stereoselective synthesis of bioactive flavanolignans, could not be reproduced. Thus, the target molecule was prepared via the synthesis and separation of diastereomeric O-glucosides. TDDFT-ECD calculations and the 1,4-benzodioxane helicity rule were utilized to determine the absolute configuration. ECD calculations also confirmed that the L-1(b) Cotton effect is governed by the helicity of the heteroring, while the higher-energy ECD transitions reflect mainly the orientation of the equatorial C-2 aryl group. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Veronika AU - Agócs, Attila AU - Deli, József AU - Gulyás, Gergely AU - Tóthné Illyés, Tünde Zita AU - Kurtán, Tibor AU - Turcsi, Erika Margit AU - Béni, Szabolcs AU - Dékány, Miklós AU - Ballot, A AU - Vasas, Gábor TI - Carotenoid glycoside isolated and identified from cyanobacterium Cylindrospermopsis raciborskii JF - JOURNAL OF FOOD COMPOSITION AND ANALYSIS J2 - J FOOD COMPOS ANAL VL - 65 PY - 2018 SP - 6 EP - 10 PG - 5 SN - 0889-1575 DO - 10.1016/j.jfca.2017.06.003 UR - https://m2.mtmt.hu/api/publication/3236025 ID - 3236025 AB - The freshwater cyanobacterium Cylindrospermopsis raciborskii was investigated for carotenoid composition. Besides β-carotene, echinenone and (9/9′Z)-echinenone a carotenoid glycoside was found to be the main component. This compound was isolated and subsequently acetylated for structural elucidation. The acetyl derivative was fully characterized by UV–vis, ECD, NMR and HRMS techniques. The detailed 1H and 13C NMR chemical shift assignment of the major carotenoid supported the unequivocal identification of (2′S)-2-hydroxymyxol 2′-α-L-fucoside. LA - English DB - MTMT ER - TY - CONF AU - Deli, József AU - Nagy, Veronika AU - Agócs, Attila AU - Gulyás-Fekete, G AU - Turcsi, Erika Margit AU - Tóthné Illyés, Tünde Zita AU - Vasas, Gábor ED - [s.n.], null TI - Carotenoid glycosides isolated and identified from cyanobacterium Cylindrospermopsis raciborskii and Nostoc sp. T2 - 18th International Symposium on Carotenoids 2017 PY - 2017 SP - 96 EP - 96 PG - 1 UR - https://m2.mtmt.hu/api/publication/3267961 ID - 3267961 N1 - [Poszter] LA - English DB - MTMT ER - TY - JOUR AU - Csávás, Magdolna AU - Malinovská, L AU - Perret, F AU - Gyurkó, M AU - Tóthné Illyés, Tünde Zita AU - Wimmerová, M AU - Borbás, Anikó TI - Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia JF - CARBOHYDRATE RESEARCH J2 - CARBOHYD RES VL - 437 PY - 2017 SP - 1 EP - 8 PG - 8 SN - 0008-6215 DO - 10.1016/j.carres.2016.11.008 UR - https://m2.mtmt.hu/api/publication/3159792 ID - 3159792 N1 - Folyóiratcikk folyóirat Hosszú név: Carbohydrate Research folyóiratcikk Befejező oldal: 8 folyóiratcikk Kezdő oldal: 1 folyóiratcikk Kötet: 437 Jelleg Műfaj: JOUR Könyvrészlet Besorolás Név: JOUR Besorolás Név: JOUR fejezet/konferencia cikk Befejező oldal: 8 fejezet/konferencia cikk Kezdő oldal: 1 Jelleg Műfaj: JOUR Jelleg Műfaj: JOUR könyv/konferencia : 437 könyv/konferencia Sorozat kötet: 437 közlemény Cím: Carbohydrate Research Könyv könyv/konferencia : 437 könyv/konferencia Sorozat cím: Carbohydrate Research könyv/konferencia Sorozat kötet: 437 közlemény Terjedelem: 1 Egyéb konferenciaközlemény fejezet/konferencia cikk Befejező oldal: 8 fejezet/konferencia cikk Kezdő oldal: 1 könyv/konferencia : 437 könyv/konferencia Sorozat kötet: 437 közlemény Cím: Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia közlemény Cím: Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia közlemény Cím: Carbohydrate Research Egyéb konferenciakötet könyv/konferencia : 437 könyv/konferencia Sorozat kötet: 437 közlemény Cím: Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia közlemény Cím: Carbohydrate Research Oltalmi formák szabadalom Benyújtás száma: 437 Disszertáció disszertáció Sorozat szám: 437 közlemény Terjedelem: 1 Besorolás: Szabad mező 1: 437 Szabad mező 2: 8 Kezdő oldal: 1 AB - The opportunistic Gram-negative bacterium Burkholderia cenocepacia causes lethal infections in cystic fibrosis patients. Multivalent mannoside derivatives were prepared as potential inhibitors of lectin BC2LA, one of the virulence factors deployed by B. cenocepacia in the infection process. An (alpha 1 -> 2)-thiolinked mannobioside mimic bearing an azide functionalized aglycon was conjugated to different multivalent scaffolds such as propargylated calix[4]arenes, methyl gallate and pentaerythritol by azidealkyne 1,3-dipolar cycloaddition. The interaction between the glycoclusters and the mannose binding BC2L-A lectin from B. cenocepacia was examined by isothermal microcalorimetry, surface plasmon resonance, inhibition of yeast agglutination and analytical ultracentrifugation. LA - English DB - MTMT ER - TY - JOUR AU - Tóthné Illyés, Tünde Zita AU - Balla, S AU - Bényei, Attila Csaba AU - Kumar, AA AU - Timári, István AU - E Kövér, Katalin AU - Szilágyi, László TI - Exploring the Syntheses of Novel Glycomimetics. Carbohydrate Derivatives with Se-S- or Se-Se- Glycosidic Linkages JF - CHEMISTRYSELECT J2 - CHEMISTRYSELECT VL - 1 PY - 2016 IS - 10 SP - 2383 EP - 2388 PG - 6 SN - 2365-6549 DO - 10.1002/slct.201600628 UR - https://m2.mtmt.hu/api/publication/3116567 ID - 3116567 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFI/OTKA NN 109671, OTKA K 105459]; Richter Gedeon Talentum Alapitvany Funding text: This research was supported by the National Research, Development and Innovation Office of Hungary (grant nos. NKFI/OTKA NN 109671 to L. Sz. and OTKA K 105459 to K. E. K.) and by the Richter Gedeon Talentum Alapitvany (Ph.D. scholarship to I.T.) AB - A convenient route to Se-S-glycoside derivatives was developed using glycosyl isoselenuronium salts as glycosylselenenyl transfer reagents toward thiols. Aliphatic and aromatic thiols were found to react in the presence of N,N-diisopropylethylamine as a base and furnished alkyl- or aryl glycosylselenenylsulfide derivatives. S-glycosylselenenyl-cysteines were obtained similarly via reactions with O,N-protected cysteine. Reactions with monosaccharide thiols provided disaccharide mimics featuring Se-S- interglycosidic bonds. Further disaccharide mimics with Se-Se interglycosidic linkage were obtained from the starting isoselenuronium salts via reactions with protected monosaccharide derivatives bearing selenol groups in 6- or 4-position. The novel glycomimetics are expected to open new perspectives in biological activities and/or mechanistic studies due, i.a., to the rather uncommon Se-S- or Se-Se bonds incorporated into a carbohydrate framework. LA - English DB - MTMT ER - TY - JOUR AU - Fehér, Krisztina AU - Timári, István AU - Rákosi, Kinga AU - Szolomájer, János AU - Tóthné Illyés, Tünde Zita AU - Bartók, Ádám AU - Varga, Zoltán AU - Panyi, György AU - Tóth, Gábor AU - E Kövér, Katalin TI - Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds JF - CHEMICAL SCIENCE J2 - CHEM SCI VL - 7 PY - 2016 IS - 4 SP - 2666 EP - 2673 PG - 8 SN - 2041-6520 DO - 10.1039/C5SC03995A UR - https://m2.mtmt.hu/api/publication/2989146 ID - 2989146 N1 - Megjegyzés-27382737 OA gold AB - Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin contg. four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve the potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chem. synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chem. synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacol. properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined exptl. and theor. approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. The use of such combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed to characterize the conformational dynamics around each disulfide/diselenide bridge. [on SciFinder(R)] LA - English DB - MTMT ER - TY - JOUR AU - József, János AU - Juhász, László AU - Tóthné Illyés, Tünde Zita AU - Csávás, Magdolna AU - Borbás, Anikó AU - Somsák, László TI - Photoinitiated hydrothiolation of pyranoid exo-glycals: the D-galacto and D-xylo cases JF - CARBOHYDRATE RESEARCH J2 - CARBOHYD RES VL - 413 PY - 2015 IS - 0 SP - 63 EP - 69 PG - 7 SN - 0008-6215 DO - 10.1016/j.carres.2015.05.008 UR - https://m2.mtmt.hu/api/publication/2906549 ID - 2906549 N1 - Megjegyzés-24978180 10.1016/j.carres.2015.05.008 AB - Radical-mediated addition reactions of thiols to O-peracetylated exo-galactal and exo-xylal with 2,2-dimethoxy-2-phenylacetophenone as the photoinitiator resulted in high yielding formation of the corresponding β-D-glycopyranosylmethyl-sulfide derivatives (2,6-anhydro-1-deoxy-1-S-substituted-1-thio-alditols) with exclusive regio- and very high stereoselectivity, including disaccharide mimicks with Gly-CH2-S-Gly scaffolds. LA - English DB - MTMT ER -