@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:34722559,
	title = {Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants},
	url = {https://m2.mtmt.hu/api/publication/34722559},
	author = {Tóth, Balázs István and Bahar, Bazeli and Annelies, Janssens and Lisztes, Erika and Racskó, Márk and Kelemen, Balázs and Herczeg, Mihály and Nagy, Tamás Milán and E Kövér, Katalin and Argha, Mitra and Attila, Borics and Bíró, Tamás and Thomas, Voets},
	journal-iso = {ELIFE},
	journal = {ELIFE},
	unique-id = {34722559},
	issn = {2050-084X},
	year = {2024},
	eissn = {2050-084X},
	orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789}
}

@article{MTMT:33699950,
	title = {Phosphorylated Peptide Derived from the Myosin Phosphatase Target Subunit Is a Novel Inhibitor of Protein Phosphatase-1},
	url = {https://m2.mtmt.hu/api/publication/33699950},
	author = {Kónya, Zoltán and Tamás, István and Bécsi, Bálint and Lontay, Beáta and Hadháziné Raics, Mária and Timári, István and E Kövér, Katalin and Erdődi, Ferenc},
	doi = {10.3390/ijms24054789},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33699950},
	issn = {1661-6596},
	abstract = {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.},
	keywords = {Molecular docking; saturation transfer difference NMR; protein phosphatase-1 (PP1); myosin phosphatase (MP); myosin phosphatase target subunit-1 (MYPT1); MYPT1 inhibitory peptide (P-Thr696-MYPT1690-701)},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Timári, István/0000-0003-0504-6967}
}

@article{MTMT:33693788,
	title = {Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis},
	url = {https://m2.mtmt.hu/api/publication/33693788},
	author = {Gönczi, Mónika and Teixeira, João M. C. and Barrera-Vilarmau, Susana and Mediani, Laura and Antoniani, Francesco and Nagy, Tamás Milán and Fehér, Krisztina and Ráduly, Zsolt and Ambrus, Viktor Attila and Tőzsér, József and Barta, Endre and E Kövér, Katalin and Csernoch, László and Carra, Serena and Fuxreiter, Mónika},
	doi = {10.1038/s41467-023-37017-7},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {14},
	unique-id = {33693788},
	issn = {2041-1723},
	abstract = {During muscle cell differentiation, the alternatively spliced, acidic β-domain potentiates transcription of Myocyte-specific Enhancer Factor 2 (Mef2D). Sequence analysis by the FuzDrop method indicates that the β-domain can serve as an interaction element for Mef2D higher-order assembly. In accord, we observed Mef2D mobile nuclear condensates in C2C12 cells, similar to those formed through liquid-liquid phase separation. In addition, we found Mef2D solid-like aggregates in the cytosol, the presence of which correlated with higher transcriptional activity. In parallel, we observed a progress in the early phase of myotube development, and higher MyoD and desmin expression. In accord with our predictions, the formation of aggregates was promoted by rigid β-domain variants, as well as by a disordered β-domain variant, capable of switching between liquid-like and solid-like higher-order states. Along these lines, NMR and molecular dynamics simulations corroborated that the β-domain can sample both ordered and disordered interactions leading to compact and extended conformations. These results suggest that β-domain fine-tunes Mef2D higher-order assembly to the cellular context, which provides a platform for myogenic regulatory factors and the transcriptional apparatus during the developmental process.},
	keywords = {CELL BIOLOGY; Structural biology; Computational biology and bioinformatics},
	year = {2023},
	eissn = {2041-1723},
	orcid-numbers = {Barta, Endre/0000-0002-6753-0714; Carra, Serena/0000-0003-0939-0140}
}

@article{MTMT:33683947,
	title = {Multifaceted Domino Knoevenagel‐Cyclization Reactions; Four Movements for 2H‐Chromenes and Chromans},
	url = {https://m2.mtmt.hu/api/publication/33683947},
	author = {Király, Sándor Balázs and Tóth, László and Kovács, Tibor and Bényei, Attila Csaba and Lisztes, Erika and Tóth, Balázs István and Bíró, Tamás and Kiss, Attila and E Kövér, Katalin and Mándi, Attila and Kurtán, Tibor},
	doi = {10.1002/adsc.202300083},
	journal-iso = {ADV SYNTH CATAL},
	journal = {ADVANCED SYNTHESIS & CATALYSIS},
	volume = {365},
	unique-id = {33683947},
	issn = {1615-4150},
	abstract = {Domino Knoevenagel-cyclization reactions of 2H-chromene and chroman derivatives containing o-formylaryl amine or ether side-chain was carried out to produce four series of chiral condensed heterocycles representing four novel skeletons and exhibiting antiproliferative activity. The cyclization step occurred with four different mechanisms: a concerted intramolecular hetero Diels-Alder reaction (IMHDA), a stepwise polar [2+2] cycloaddition, a [1,5]-hydride shift-6-endo cyclization or a multi-step nitro hetero Diels-Alder-ring-opening-Cadogan-type cyclization sequence. The latter reaction provided a new route to hydroxyindoles by an inverse Cadogan-type cyclization, in which the nitro group is deoxygenated by a nitro IMHDA-ring-opening sequence. The cyclization mechanisms and their stereoselectivity were studied by DFT calculations, based on which we proposed a mechanism for the multi-step cyclization to hydroxyindoles and explained the observed diastereoselectivity.},
	keywords = {HETEROCYCLES; configuration determination; diastereoselectivity; domino reactions; cycloaddition; MOLECULAR DIVERSITY},
	year = {2023},
	eissn = {1615-4169},
	pages = {3301-3319},
	orcid-numbers = {Kiss, Attila/0000-0003-3601-5143}
}

@article{MTMT:33550734,
	title = {DMSO-Induced Unfolding of the Antifungal Disulfide Protein PAF and Its Inactive Variant: A Combined NMR and DSC Study},
	url = {https://m2.mtmt.hu/api/publication/33550734},
	author = {Czajlik, András and Batta, Ágnes and Kerner, Kinga and Fizil, Ádám and Hajdu, Dorottya Zsuzsanna and Hadháziné Raics, Mária and E Kövér, Katalin and Batta, Gyula},
	doi = {10.3390/ijms24021208},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33550734},
	issn = {1661-6596},
	abstract = {PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3–4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact. To explore such equilibria during dimethyl sulfoxide (DMSO)-induced chemical unfolding, we studied PAF and its inactive variant PAFD19S using nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). According to the NMR monitoring at 310 K, the folded structures disappear above 80 v/v% DMSO concentration, while the unfolding is completely reversible. Evaluation of a few resolved peaks from viscosity-compensated 15N-1H HSQC spectra of PAF yielded ∆G = 23 ± 7 kJ/M as the average value for NMR unfolding enthalpy. The NMR-based structures of PAF and the mutant in 50 v/v% DMSO/H2O mixtures were more similar in the mixed solvents then they were in water. The 15N NMR relaxation dynamics in the same mixtures verified the rigid backbones of the NMR-visible fractions of the proteins; still, enhanced dynamics around the termini and some loops were observed. DSC monitoring of the Tm melting point showed parabolic dependence on the DMSO molar fraction and suggested that PAF is more stable than the inactive PAFD19S. The DSC experiments were irreversible due to the applied broad temperature range, but still suggestive of the endothermic unfolding of PAF.},
	keywords = {PAF; disulfide bond; Differential scanning calorimetry (DSC); ANTIFUNGAL PROTEIN; nuclear magnetic resonance (NMR); DMSO-induced unfolding},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Fizil, Ádám/0000-0002-4815-5744; Batta, Gyula/0000-0002-0442-1828}
}

@article{MTMT:33554482,
	title = {A Fucosylated Lactose-Presenting Tetravalent Glycocluster Acting as a Mutual Ligand of Pseudomonas aeruginosa Lectins A (PA-IL) and B (PA-IIL)-Synthesis and Interaction Studies},
	url = {https://m2.mtmt.hu/api/publication/33554482},
	author = {Csávás, Magdolna and Kalmár, László and Szoke, Petronella and Farkas, László Bence and Bécsi, Bálint and Kónya, Zoltán and Kerékgyártó, János and Borbás, Anikó and Erdődi, Ferenc and E Kövér, Katalin},
	doi = {10.3390/ijms232416194},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {33554482},
	issn = {1661-6596},
	abstract = {The Gram-negative bacterium Pseudomonas aeruginosa is an important opportunistic human pathogen associated with cystic fibrosis. P. aeruginosa produces two soluble lectins, the d-galactose-specific lectin PA-IL (LecA) and the l-fucose-specific lectin PA-IIL (LecB), among other virulence factors. These lectins play an important role in the adhesion to host cells and biofilm formation. Moreover, PA-IL is cytotoxic to respiratory cells in the primary culture. Therefore, these lectins are promising therapeutic targets. Specifically, carbohydrate-based compounds could inhibit their activity. In the present work, a 3-O-fucosyl lactose-containing tetravalent glycocluster was synthesized and utilized as a mutual ligand of galactophilic and fucophilic lectins. Pentaerythritol equipped with azido ethylene glycol-linkers was chosen as a multivalent scaffold and the glycocluster was constructed by coupling the scaffold with propargyl 3-O-fucosyl lactoside using an azide-alkyne 1,3-dipolar cycloaddition reaction. The interactions between the glycocluster and PA-IL or PA-IIL were investigated by isothermal titration microcalorimetry and saturation transfer difference NMR spectroscopy. These results may assist in the development of efficient anti-adhesion therapy for the treatment of a P. aeruginosa infection.},
	keywords = {lectin; Pseudomonas aeruginosa; Multivalency; saturation transfer difference NMR; fucosylated lactose},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33332835,
	title = {Synthesis of a Heparinoid Pentasaccharide Containing L-Guluronic Acid Instead of L-Iduronic Acid with Preserved Anticoagulant Activity},
	url = {https://m2.mtmt.hu/api/publication/33332835},
	author = {Herczeg, Mihály and Demeter, Fruzsina and Lisztes, Erika and Racskó, Márk and Tóth, Balázs István and Timári, István and Bereczky, Zsuzsanna and E Kövér, Katalin and Borbás, Anikó},
	doi = {10.1021/acs.joc.2c01928},
	journal-iso = {J ORG CHEM},
	journal = {JOURNAL OF ORGANIC CHEMISTRY},
	volume = {87},
	unique-id = {33332835},
	issn = {0022-3263},
	abstract = {L-Iduronic acid is a key constituent of heparin and heparan sulfate polysaccharides due to its unique conformational plasticity, which facilitates the binding of polysaccharides to proteins. At the same time, this is the synthetically most challenging unit of heparinoid oligosaccharides; therefore, there is a high demand for its replacement with a more easily accessible sugar unit. In the case of idraparinux, an excellent anticoagulant heparinoid pentasaccharide, we demonstrated that L-iduronic acid can be replaced by an easier-to-produce L-sugar while maintaining its essential biological activity. From the inexpensive D-mannose, through a highly functionalized phenylthio mannoside, the L-gulose donor was prepared by C-5 epimerization in 10 steps with excellent yield. This unit was incorporated into the pentasaccharide by alpha-selective glycosylation and oxidized to L-guluronic acid. The complete synthesis required only 36 steps, with 21 steps for the longest linear route. The guluronate containing pentasaccharide inhibited coagulation factor Xa by 50% relative to the parent compound, representing an excellent anticoagulant activity. To the best of our knowledge, this is the first biologically active heparinoid anticoagulant which contains a different sugar unit instead of L-iduronic acid.},
	year = {2022},
	eissn = {1520-6904},
	pages = {15830-15836},
	orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Bereczky, Zsuzsanna/0000-0002-1483-3703; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33258379,
	title = {Ultrahigh-Resolution Homo- and Heterodecoupled 1H and TOCSY NMR Experiments},
	url = {https://m2.mtmt.hu/api/publication/33258379},
	author = {Timári, István and Bagi, Péter and Keglevich, György and E Kövér, Katalin},
	doi = {10.1021/acsomega.2c06102},
	journal-iso = {ACS OMEGA},
	journal = {ACS OMEGA},
	volume = {7},
	unique-id = {33258379},
	issn = {2470-1343},
	abstract = {The original homonuclear decoupled (pure shift) experiments provide ultrahigh-resolution 1H spectra of compounds containing NMR-active heteronuclei of low natural isotopic abundance (e.g., 13C or 15N). In contrast, molecules containing highly abundant heteronuclei (like 31P or 19F) give doublets or a multiple of doublets in their homonuclear decoupled spectra, depending on the number of heteronuclear coupling partners and the magnitude of the respective coupling constants. In these cases, the complex and frequently overlapping signals may hamper the unambiguous assignment of resonances. Here, we present new heteronuclear decoupled (HD) PSYCHE 1H and TOCSY experiments, which result in simplified spectra with significantly increased resolution, allowing the reliable assessment of individual resonances. The utility of the experiments has been demonstrated on a challenging stereoisomeric mixture of a platinum–phosphine complex, where ultrahigh resolution of the obtained HD PSYCHE spectra made the structure elucidation of the chiral products feasible. HD PSYCHE methods can be potentially applied to other important 31P- or 19F-containing compounds in medicinal chemistry and metabolomics.},
	year = {2022},
	eissn = {2470-1343},
	pages = {43283-43289},
	orcid-numbers = {Bagi, Péter/0000-0002-9043-6435}
}

@article{MTMT:33090799,
	title = {Four-in-one: HSQC, HSQC-TOCSY (or H2BC), TOCSY, and enhanced HMBC spectra integrated into a single NO Relaxation Delay (NORD) NMR experiment},
	url = {https://m2.mtmt.hu/api/publication/33090799},
	author = {Farkas, László Bence and Timári, István and E Kövér, Katalin and Sørensen, Ole W.},
	doi = {10.1016/j.jmr.2022.107297},
	journal-iso = {J MAGN RESON},
	journal = {JOURNAL OF MAGNETIC RESONANCE},
	volume = {343},
	unique-id = {33090799},
	issn = {1090-7807},
	abstract = {The NMR pulse sequence design strategy of NORD (NO Relaxation Delay) is extended to design of two new three-module experiments, NORD {HMBC}-{HSQC-TOCSY}-{TOCSY} and NORD {HMBC}-{2BOB}-{TOCSY}, each delivering four spectra - HMBC, HSQC, TOCSY, and either HSQC-TOCSY or H2BC. Compared to individual recording of these spectra particularly the sensitivity of the least sensitive mod-ule, HMBC, is enhanced by designing the homonuclear TOCSY module to allow buildup of magnetization pertinent to HMBC during its execution. Effectively, the sensitivity of the heteronuclear modules is boosted at the expense of the inherently much higher TOCSY sensitivity, thus resulting in a significant saving in spectrometer time.},
	keywords = {TOCSY; HMBC; HSQC-TOCSY; NORD spectroscopy; BANGO; TIG-BIRD; 2BOB},
	year = {2022},
	eissn = {1096-0856}
}