@article{MTMT:34743720, title = {Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity}, url = {https://m2.mtmt.hu/api/publication/34743720}, author = {Dibello, Estefanía and Oddone, Natalia and Franco, Jaime and Tóthné Illyés, Tünde Zita and Medeiros, Andrea and Kiss, Attila and Hőgye, Fanni and E Kövér, Katalin and Szilágyi, László and Comini, Marcelo A.}, doi = {10.1016/j.ijpddr.2024.100529}, journal-iso = {INT J PARASITOL-DRUG}, journal = {INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE}, volume = {24}, unique-id = {34743720}, issn = {2211-3207}, abstract = {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.}, keywords = {MACROPHAGE; Selenoglycosides; Redox biosensor; Oxidative stress; Bloodstream trypanosoma}, year = {2024}, eissn = {2211-3207}, orcid-numbers = {Dibello, Estefanía/0000-0001-6378-3899; Oddone, Natalia/0009-0006-4884-9398; Kiss, Attila/0000-0003-3601-5143; Comini, Marcelo A./0000-0001-5000-1333} } @article{MTMT:34567562, title = {Saturation Transfer Difference NMR and Molecular Docking Interaction Study of Aralkyl-Thiodigalactosides as Potential Inhibitors of the Human-Galectin-3 Protein}, url = {https://m2.mtmt.hu/api/publication/34567562}, author = {Hőgye, Fanni and Farkas, László Bence and Balogh, Álex Kálmán and Szilágyi, László and Alnukari, Samar and Bajza, István and Borbás, Anikó and Fehér, Krisztina and Tóthné Illyés, Tünde Zita and Timári, István}, doi = {10.3390/ijms25031742}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34567562}, issn = {1661-6596}, abstract = {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.}, keywords = {lectin; NMR spectroscopy; Galectin-3; Molecular docking; STD NMR; thiodigalactosides}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:31845447, title = {Synthesis of Tetravalent Thio- and Selenogalactoside-Presenting Galactoclusters and Their Interactions with Bacterial Lectin PA-IL from Pseudomonas aeruginosa}, url = {https://m2.mtmt.hu/api/publication/31845447}, author = {Tóthné Illyés, Tünde Zita and Malinovská, Lenka and Rőth, Erzsébet and Tóth, Boglárka and Farkas, László Bence and Korsák, Marek and Wimmerová, Michaela and E Kövér, Katalin and Csávás, Magdolna}, doi = {10.3390/molecules26030542}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {26}, unique-id = {31845447}, issn = {1420-3049}, abstract = {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.}, keywords = {Pseudomonas aeruginosa; Selenoglycosides; Multivalency; galactoclusters; PA-IL lectin}, year = {2021}, eissn = {1420-3049}, orcid-numbers = {Malinovská, Lenka/0000-0002-4211-3033; Korsák, Marek/0000-0001-7357-5321; Wimmerová, Michaela/0000-0002-7108-4198; E Kövér, Katalin/0000-0001-5020-4456} } @article{MTMT:31149376, title = {Evaluation of Different Synthetic Routes to (2R,3R)-3-Hydroxymethyl-2-(4-hydroxy-3-methoxyphenyl)-1,4-Benzodioxane-6 -Carbaldehyde}, url = {https://m2.mtmt.hu/api/publication/31149376}, author = {Ferenczi, Renata Kertine and Tóthné Illyés, Tünde Zita and Király, Sándor Balázs and Hoffka, Gyula and Szilágyi, László and Mándi, Attila and Antus, Sándor and Kurtán, Tibor}, doi = {10.2174/1385272823666191212113407}, journal-iso = {CURR ORG CHEM}, journal = {CURRENT ORGANIC CHEMISTRY}, volume = {23}, unique-id = {31149376}, issn = {1385-2728}, abstract = {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.}, keywords = {STEREOSELECTIVE SYNTHESIS; STEREOCHEMISTRY; Chemistry; SILYMARIN; Absolute configuration; FLAVONOLIGNANS; ISOSILYBIN; SILYBUM-MARIANUM; TDDFT-ECD calculation; 1,4-benzodioxane; flavanolignans; SILIBININ DIASTEREOMERS}, year = {2019}, eissn = {1875-5348}, pages = {2960-2968} } @article{MTMT:3236025, title = {Carotenoid glycoside isolated and identified from cyanobacterium Cylindrospermopsis raciborskii}, url = {https://m2.mtmt.hu/api/publication/3236025}, author = {Nagy, Veronika and Agócs, Attila and Deli, József and Gulyás, Gergely and Tóthné Illyés, Tünde Zita and Kurtán, Tibor and Turcsi, Erika Margit and Béni, Szabolcs and Dékány, Miklós and Ballot, A and Vasas, Gábor}, doi = {10.1016/j.jfca.2017.06.003}, journal-iso = {J FOOD COMPOS ANAL}, journal = {JOURNAL OF FOOD COMPOSITION AND ANALYSIS}, volume = {65}, unique-id = {3236025}, issn = {0889-1575}, abstract = {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.}, keywords = {NMR; Cylindrospermopsis raciborskii; cyanobacterium; Blue-green algae; 2-hydroxymyxol fucoside; Carotenoid glycoside}, year = {2018}, eissn = {1096-0481}, pages = {6-10}, orcid-numbers = {Nagy, Veronika/0000-0002-9019-7980; Deli, József/0000-0002-0625-6117; Béni, Szabolcs/0000-0001-7056-6825} } @CONFERENCE{MTMT:3267961, title = {Carotenoid glycosides isolated and identified from cyanobacterium Cylindrospermopsis raciborskii and Nostoc sp.}, url = {https://m2.mtmt.hu/api/publication/3267961}, author = {Deli, József and Nagy, Veronika and Agócs, Attila and Gulyás-Fekete, G and Turcsi, Erika Margit and Tóthné Illyés, Tünde Zita and Vasas, Gábor}, booktitle = {18th International Symposium on Carotenoids 2017}, unique-id = {3267961}, year = {2017}, pages = {96-96}, orcid-numbers = {Deli, József/0000-0002-0625-6117; Nagy, Veronika/0000-0002-9019-7980} } @article{MTMT:3159792, title = {Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia}, url = {https://m2.mtmt.hu/api/publication/3159792}, author = {Csávás, Magdolna and Malinovská, L and Perret, F and Gyurkó, M and Tóthné Illyés, Tünde Zita and Wimmerová, M and Borbás, Anikó}, doi = {10.1016/j.carres.2016.11.008}, journal-iso = {CARBOHYD RES}, journal = {CARBOHYDRATE RESEARCH}, volume = {437}, unique-id = {3159792}, issn = {0008-6215}, abstract = {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.}, keywords = {Click reaction; MANNOSE-BINDING LECTIN; Burkholderia cenocepacia; Anti-adhesion therapy; glycoclusters}, year = {2017}, eissn = {1873-426X}, pages = {1-8}, orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:3116567, title = {Exploring the Syntheses of Novel Glycomimetics. Carbohydrate Derivatives with Se-S- or Se-Se- Glycosidic Linkages}, url = {https://m2.mtmt.hu/api/publication/3116567}, author = {Tóthné Illyés, Tünde Zita and Balla, S and Bényei, Attila Csaba and Kumar, AA and Timári, István and E Kövér, Katalin and Szilágyi, László}, doi = {10.1002/slct.201600628}, journal-iso = {CHEMISTRYSELECT}, journal = {CHEMISTRYSELECT}, volume = {1}, unique-id = {3116567}, issn = {2365-6549}, abstract = {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.}, keywords = {Carbohydrate; selenenylsulfide; selenosugar; Se-Se-bond}, year = {2016}, eissn = {2365-6549}, pages = {2383-2388} } @article{MTMT:2989146, title = {Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds}, url = {https://m2.mtmt.hu/api/publication/2989146}, author = {Fehér, Krisztina and Timári, István and Rákosi, Kinga and Szolomájer, János and Tóthné Illyés, Tünde Zita and Bartók, Ádám and Varga, Zoltán and Panyi, György and Tóth, Gábor and E Kövér, Katalin}, doi = {10.1039/C5SC03995A}, journal-iso = {CHEM SCI}, journal = {CHEMICAL SCIENCE}, volume = {7}, unique-id = {2989146}, issn = {2041-6520}, abstract = {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)]}, year = {2016}, eissn = {2041-6539}, pages = {2666-2673}, orcid-numbers = {Szolomájer, János/0000-0003-1458-6156; Bartók, Ádám/0000-0002-1232-5246; Panyi, György/0000-0001-6227-3301; Tóth, Gábor/0000-0002-3604-4385} } @article{MTMT:2906549, title = {Photoinitiated hydrothiolation of pyranoid exo-glycals: the D-galacto and D-xylo cases}, url = {https://m2.mtmt.hu/api/publication/2906549}, author = {József, János and Juhász, László and Tóthné Illyés, Tünde Zita and Csávás, Magdolna and Borbás, Anikó and Somsák, László}, doi = {10.1016/j.carres.2015.05.008}, journal-iso = {CARBOHYD RES}, journal = {CARBOHYDRATE RESEARCH}, volume = {413}, unique-id = {2906549}, issn = {0008-6215}, abstract = {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.}, keywords = {Disaccharide mimicks; Exo-xylal; Exo-galactal; Thiol-ene click reaction}, year = {2015}, eissn = {1873-426X}, pages = {63-69}, orcid-numbers = {Juhász, László/0000-0002-7462-7944; Borbás, Anikó/0000-0001-8462-4547; Somsák, László/0000-0002-9103-9845} }