@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:32859682, title = {Synthesis of Four Orthogonally Protected Rare l-Hexose Thioglycosides from d-Mannose by C-5 and C-4 Epimerization}, url = {https://m2.mtmt.hu/api/publication/32859682}, author = {Demeter, Fruzsina and Bakai-Bereczki, Ilona and Borbás, Anikó and Herczeg, Mihály}, doi = {10.3390/molecules27113422}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {27}, unique-id = {32859682}, issn = {1420-3049}, abstract = {l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural sources and due to the complexity of their synthesis, their commercially available derivatives are also very expensive. Starting from one of the cheapest d-hexoses, d-mannose, using inexpensive and readily available chemicals, we developed a reaction pathway to obtain two orthogonally protected l-hexose thioglycoside derivatives, l-gulose and l-galactose, through the corresponding 5,6-unsaturated thioglycosides by C-5 epimerization. From these derivatives, the orthogonally protected thioglycosides of further two l-hexoses (l-allose and l-glucose) were synthesized by C-4 epimerization. The preparation of the key intermediates, the 5,6-unsaturated derivatives, was systematically studied using various protecting groups. By the method developed, we are able to produce highly functionalized l-gulose derivatives in 9 steps (total yields: 21-23%) and l-galactose derivatives in 12 steps (total yields: 6-8%) starting from d-mannose.}, year = {2022}, eissn = {1420-3049}, orcid-numbers = {Bakai-Bereczki, Ilona/0000-0003-4601-7257; Borbás, Anikó/0000-0001-8462-4547; Herczeg, Mihály/0000-0002-7938-9789} } @article{MTMT:32430281, title = {Systematic Study of Regioselective Reductive Ring-Opening Reactions of 4,6-O-Halobenzylidene Acetals of Glucopyranosides}, url = {https://m2.mtmt.hu/api/publication/32430281}, author = {Mező, Erika and Herczeg, Mihály and Demeter, Fruzsina and Bakai-Bereczki, Ilona and Csávás, Magdolna and Borbás, Anikó}, doi = {10.1021/acs.joc.1c01667}, journal-iso = {J ORG CHEM}, journal = {JOURNAL OF ORGANIC CHEMISTRY}, volume = {86}, unique-id = {32430281}, issn = {0022-3263}, abstract = {Reductive openings of cyclic acetals are widely used in modern synthetic organic chemistry for the regioselective introduction of protecting groups. A systematic study was performed on the applicability and efficacy of various hydride donor and protic or Lewis acid reagent combinations in the reductive ring opening of glucosidic 4,6-halobenzylidene acetals bearing an ortho-, meta-, and para-chloro- or -bromo substituent on the benzene ring. Most of the reagent combinations tested cleaved the 4,6-O-halobenzylidene acetal rings at O4 or O6 efficiently and with the expected regioselectivity. The LiAlH4-AlCl3 and the BH3 center dot THF-TMSOTf combinations produced the 4-O-halobenzyl ether/6-OH products with complete regioselectivity and high yields. The use of Me3N center dot BH3-AlCl3 reagent system in toluene was also effective in cleaving the acetal ring at O6 but was accompanied by Al-chelation-assisted debenzylation side reactions. The NaCNBH3-HCl and the Et3SiH-BF3 center dot Et2O combinations were highly effective in yielding the 6-halobenzyl ether/4-OH derivatives. Et3SiH, in combination with TfOH, produced the 6-O-ether/4-OH products in rapid reactions but also triggered silylation and reductive halobenzylation as secondary transformations. Reductive opening of the 1,3-dioxane ring of pyranosidic 4,6-O-halobenzylidene acetals by the proper reagent combination was found to be an efficient method for the regioselective introduction of versatile halobenzyl protecting groups onto the pyranose ring.}, year = {2021}, eissn = {1520-6904}, pages = {12973-12987}, orcid-numbers = {Mező, Erika/0000-0002-8329-6745; Herczeg, Mihály/0000-0002-7938-9789; Bakai-Bereczki, Ilona/0000-0003-4601-7257; Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:32370822, title = {Tightly linked morpholino-nucleoside chimeras: new, compact cationic oligonucleotide analogues}, url = {https://m2.mtmt.hu/api/publication/32370822}, author = {Debreczeni, Nóra and Bege, Miklós and Herczeg, Mihály and Bakai-Bereczki, Ilona and Batta, Gyula and Herczegh, Pál and Borbás, Anikó}, doi = {10.1039/d1ob01174j}, journal-iso = {ORG BIOMOL CHEM}, journal = {ORGANIC & BIOMOLECULAR CHEMISTRY}, volume = {19}, unique-id = {32370822}, issn = {1477-0520}, abstract = {The polyanionic phosphodiester backbone of nucleic acids contributes to high nuclease sensitivity and low cellular uptake and is therefore a major obstacle to the biological application of native oligonucleotides. Backbone modifications, particularly charge alterations is a proven strategy to provide artificial oligonucleotides with improved properties. Here, we describe the synthesis of a new type of oligonucleotide analogues consisting of a morpholino and a ribo- or deoxyribonucleoside in which the 5 '-amino group of the nucleoside unit provides the nitrogen of the morpholine ring. The synthetic protocol is compatible with trityl and dimethoxytrityl protecting groups and azido functionality, and was extended to the synthesis of higher oligomers. The chimeras are positively charged in aqueous medium, due to the N-alkylated tertiary amine structure of the morpholino unit.}, year = {2021}, eissn = {1477-0539}, pages = {8711-8721}, orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Bakai-Bereczki, Ilona/0000-0003-4601-7257; Batta, Gyula/0000-0002-0442-1828; Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:32217410, title = {Conformational Analysis of Heparin-Analogue Pentasaccharides by Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulations}, url = {https://m2.mtmt.hu/api/publication/32217410}, author = {Balogh, Gábor and Gyöngyösi, Tamás and Timári, István and Herczeg, Mihály and Borbás, Anikó and Sadiq, S. Kashif and Fehér, Krisztina and E Kövér, Katalin}, doi = {10.1021/acs.jcim.1c00200}, journal-iso = {J CHEM INF MODEL}, journal = {JOURNAL OF CHEMICAL INFORMATION AND MODELING}, volume = {61}, unique-id = {32217410}, issn = {1549-9596}, year = {2021}, eissn = {1549-960X}, pages = {2926-2936}, orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:31828951, title = {Synthesis and cell growth inhibitory activity of six non‐glycosaminoglycan‐type heparin‐analogue trisaccharides}, url = {https://m2.mtmt.hu/api/publication/31828951}, author = {Lisztes, Erika and Mező, Erika and Demeter, Fruzsina and Horváth, Lilla and Bősze, Szilvia and Tóth, Balázs István and Borbás, Anikó and Herczeg, Mihály}, doi = {10.1002/cmdc.202000917}, journal-iso = {CHEMMEDCHEM}, journal = {CHEMMEDCHEM}, volume = {16}, unique-id = {31828951}, issn = {1860-7179}, abstract = {The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Here, we present the efficient synthesis of five Glc‐GlcA‐Glc sequenced and one Glc‐IdoA‐Glc sequenced non‐glycosaminoglycan, heparin‐related trisaccharides with various sulfation/sulfonylation and methylation patterns. The cell growth inhibitory effects of the compounds were tested against four cancerous human cell lines and two non‐cancerous cell lines. Two D‐glucuronate‐containing tetra‐ O ‐sulfated, partially methylated trisaccharides displayed remarkable and selective cell growth inhibitory effects on ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental while acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives.}, keywords = {synthesis; HEPARIN; Antitumor activity; Trisaccharides; human cells}, year = {2021}, eissn = {1860-7187}, pages = {1467-1476}, orcid-numbers = {Mező, Erika/0000-0002-8329-6745; Borbás, Anikó/0000-0001-8462-4547; Herczeg, Mihály/0000-0002-7938-9789} } @article{MTMT:31624160, title = {Synthesis of alpha-1,2-and alpha-1,3-linked di-rhamnolipids for biological studies}, url = {https://m2.mtmt.hu/api/publication/31624160}, author = {Demeter, Fruzsina and Chang, Margaret Dah-Tsyr and Lee, Yuan-Chuan and Fu, Tse-Kai and Herczeg, Mihály and Borbás, Anikó}, doi = {10.1016/j.carres.2020.108102}, journal-iso = {CARBOHYD RES}, journal = {CARBOHYDRATE RESEARCH}, volume = {496}, unique-id = {31624160}, issn = {0008-6215}, abstract = {For a detailed examination of the interaction of rhamnose containing derivatives with recombinant horseshoe crab plasma lectin (rHPL), two di-rhamno-di-lipids (an alpha-1,2- and an alpha-1,3-linked) were synthesized via a new simple method. The N-iodosuccinimide/triflic acid mediated glycosylation of the methyl (R)-3-hydroxydecanoate with phenyl-1-thio-rhamnobioside donors afforded the mono-lipid disaccharides. Removal of the methyl ester group followed by esterification of the mono-lipids with a second (R)-3-hydroxydecanoate unit resulted in fully protected di-lipid derivatives, transformation of which into the target compounds was accomplished in two steps. This method allows the synthesis of both regioisomers in only 6 steps starting from the corresponding free disaccharides. Both synthetic di-rhamnolipids were biologically active for lectin binding differential binding preference between two isomeric di-rhamno-di-lipids. The rHPL lectin favours the alpha-1,3-linked di-rhamno-di-lipids over its alpha-1,2-linked regioisomer.}, keywords = {decanoic acid; Chemistry, Applied; Biochemistry & Molecular Biology; Glycolipids; Stereoselective glycosylation; L-rhamnose}, year = {2020}, eissn = {1873-426X}, orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:31157343, title = {Photoinitiated Thiol‐Ene Reactions of Various 2,3‐Unsaturated O‐, C‐ S‐ and N‐Glycosides – Scope and Limitations Study}, url = {https://m2.mtmt.hu/api/publication/31157343}, author = {Kelemen, Viktor and Csávás, Magdolna and Hotzi, Judit and Herczeg, Mihály and Singh, Poonam and Rathi, Brijesh and Herczegh, Pál and Jain, Nidhi and Borbás, Anikó}, doi = {10.1002/asia.201901560}, journal-iso = {CHEM-ASIAN J}, journal = {CHEMISTRY-AN ASIAN JOURNAL}, volume = {15}, unique-id = {31157343}, issn = {1861-4728}, year = {2020}, eissn = {1861-471X}, pages = {876-891}, orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:31154422, title = {An Efficient Synthesis of the Pentasaccharide Repeating Unit of Pseudomonas aeruginosa Psl Exopolysaccharide}, url = {https://m2.mtmt.hu/api/publication/31154422}, author = {Demeter, Fruzsina and Chang, Margaret Dah-Tsyr and Lee, Yuan-Chuan and Borbás, Anikó and Herczeg, Mihály}, doi = {10.1055/s-0039-1690747}, journal-iso = {SYNLETT}, journal = {SYNLETT}, volume = {31}, unique-id = {31154422}, issn = {0936-5214}, abstract = {Pseudomonas aeruginosa is a biofilm-forming Gram-negative bacterium and a leading cause of life-threatening nosocomial infections. The polysaccharide synthesis locus (Psl) exopolysaccharide of P. aeruginosa is a key constituent of the defending bacterial biofilm layer and is a promising therapeutic target for resistant species. The Psl exopolysaccharide is built up from repeating pentasaccharide units which contain one α- and two β-mannosidic linkages, and one l-rhamnose and one d-glucose moieties. The preparation of this pentasaccharide was first described by Boons et al. in a 34-step synthesis. Based on their work, we have developed a new and effective pathway for the synthesis of the repeating pentasaccharide unit of the Psl exopolysaccharide. We have succeeded in simplifying the synthesis of the l-rhamnose and the α-selective d-mannose building blocks. Furthermore, taking advantage of a chemoselective pre-activation-based β-mannosylation, we directly prepare a thioglycoside disaccharide donor and use it in the next coupling reaction without further transformation. The pentasaccharide, in the form of a p-methoxyphenyl glycoside, is prepared in 26 steps, which is suitable for biological testing.}, year = {2020}, eissn = {1437-2096}, pages = {469-474}, orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547; Herczeg, Mihály/0000-0002-7938-9789} } @article{MTMT:30947204, title = {Comparison of Carbohydrate Force Fields Using Gaussian Accelerated Molecular Dynamics Simulations and Development of Force Field Parameters for Heparin-Analogue Pentasaccharides}, url = {https://m2.mtmt.hu/api/publication/30947204}, author = {Balogh, Gábor and Gyöngyösi, Tamás and Timári, István and Herczeg, Mihály and Borbás, Anikó and Fehér, Krisztina and E Kövér, Katalin}, doi = {10.1021/acs.jcim.9b00666}, journal-iso = {J CHEM INF MODEL}, journal = {JOURNAL OF CHEMICAL INFORMATION AND MODELING}, volume = {59}, unique-id = {30947204}, issn = {1549-9596}, abstract = {Computational description of conformational and dynamic properties of anticoagulant heparin analogue pentasaccharides is of crucial importance in understanding their biological activities. We designed and synthesized idraparinux derivatives modified with sulfonatomethyl moieties at the D, F, and H glucose units that display varied potencies depending on the exact nature of the substitution. In this report we examined the capability of molecular dynamics (MD) simulations to describe the conformational behavior of these novel idraparinux derivatives. We used Gaussian accelerated MD (GAMD) simulations on the parent compound, idraparinux, to choose the most suitable carbohydrate force field for these type of compounds. GAMD provided significant acceleration of conformational transitions compared to classical MD. We compared descriptors obtained from GAMD with NMR spectroscopic parameters related to geometrical descriptors such as scalar couplings and nuclear Overhauser effects (NOE) measured on idraparinux. We found that the experimental data of idraparinux is best reproduced by the CHARMM carbohydrate force field. Furthermore, we propose a torsion angle parameter for the sulfonato-methyl group, which was developed for the chosen CHARMM force field using quantum chemical calculations and validated by comparison with NMR data. The work lays down the foundation of using MD simulations to gain insight into the conformational properties of sulfonato-methyl group modified idraparinux derivatives and to understand their structure–activity relationship thus enabling rational design of further modifications.}, year = {2019}, eissn = {1549-960X}, pages = {4855-4867}, orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Borbás, Anikó/0000-0001-8462-4547} }