Block Synthesis and Step-Growth Polymerization of C-6-Sulfonatomethyl-Containing Sulfated Malto-Oligosaccharides and Their Biological Profiling

• Published in: International journal of molecular sciences Vol. 25; no. 1; p. 677
• Main Authors: Herczeg, Mihály, Demeter, Fruzsina, Nagy, Tibor, Rusznyák, Ágnes, Hodek, Jan, Sipos, Éva, Lekli, István, Fenyvesi, Ferenc, Weber, Jan, Kéki, Sándor, Borbás, Anikó
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024; MDPI
• Subjects: Acids; Anti-Inflammatory Agents - pharmacology; anti-inflammatory effect; Anticoagulants; Antiviral agents; Antiviral Agents - pharmacology; Chromatography; Computer software industry; glycosylation; Growth; Health aspects; Heparan sulfate; malto-oligomers; Metastasis; Oligomers; Oligosaccharides - pharmacology; Polymerization; Sulfates; sulfonic acid; Sulfonic Acids; Hungary; Serbia; United States; Massachusetts; Germany; polymerization; glycosylation; malto-oligomers; anti-inflammatory effect; sulfonic acid
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25010677

Highly sulfated malto-oligomers, similar to heparin and heparan-sulfate, have good antiviral, antimetastatic, anti-inflammatory and cell growth inhibitory effects. Due to their broad biological activities and simple structure, sulfated malto-oligomer derivatives have a great therapeutic potential, therefore, the development of efficient synthesis methods for their production is of utmost importance. In this work, preparation of α-(1→4)-linked oligoglucosides containing a sulfonatomethyl moiety at position C-6 of each glucose unit was studied by different approaches. Malto-oligomeric sulfonic acid derivatives up to dodecasaccharides were prepared by polymerization using different protecting groups, and the composition of the product mixtures was analyzed by MALDI-MS methods and size-exclusion chromatography. Synthesis of lower oligomers was also accomplished by stepwise and block synthetic methods, and then the oligosaccharide products were persulfated. The antiviral, anti-inflammatory and cell growth inhibitory activity of the fully sulfated malto-oligosaccharide sulfonic acids were determined by in vitro tests. Four tested di- and trisaccharide sulfonic acids effectively inhibited the activation of the TNF-α-mediated inflammatory pathway without showing cytotoxicity.