New synthesis of oligosaccharides modelling the M epitope of the Brucella O-polysaccharide

• Published in: Frontiers in chemistry 2024-06, Vol.12, p.1424157
• Main Authors: Tsvetkov, Yury E, Volkov, Timur M, Eremin, Sergei A, Sklyarov, Oleg D, Kulakov, Yuri K, Krylov, Vadim B, Nifantiev, Nikolay E
• Format: Article
• Language: English
• Subjects: 4,6-dideoxy-D-mannose; 4-formamido; Brucella; Chemistry; lipopolysaccharide; M epitope; O-polysaccharide
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2024.1424157

Brucellosis is a dangerous zoonotic disease caused by bacteria of the genus . Diagnosis of brucellosis is based on the detection in animal and human sera of antibodies to the O-polysaccharide of lipopolysaccharide. The currently employed serodiagnosis of brucellosis relies on the use of the O-polysaccharide as a diagnostic antigen. However, the existence of bacterial species, which also express O-polysaccharides structurally similar to that of , may decrease the specificity of the brucellosis detection due to false-positive test results. It has been shown that the efficiency of the test can be significantly improved by using synthetic oligosaccharides that correspond to the so-called M epitope of the O-antigen. This epitope is characterized by an α-(1→3)-linkage between d-perosamine units and is unique to . Here we report on an efficient approach to the synthesis of oligosaccharides that model the M epitope of the O-polysaccharide. The approach is based on the use of the α-(1→3)-linked disaccharide thioglycoside as the key donor block. Its application allowed the straightforward assembly of a set of four protected oligosaccharides, which includes a disaccharide, two trisaccharides, and a tetrasaccharide, in five glycosylation steps. The synthesized oligosaccharides are planned to be used in the development of diagnostic tools for identifying brucellosis in humans and domestic animals, as well as a potential vaccine against it.