CONFERENCE PROCEEDING
Synthesis of oligosaccharides related to cryptococcus neoformans galactoxylomannan fragments
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N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Publication date: 2024-11-26
Public Health Toxicol 2024;4(Supplement Supplement 2):A21
KEYWORDS
ABSTRACT
Introduction:
Cryptococcus neoformans is a fungal human pathogen that causes severe diseases in immunocompromised patients (especially those with HIV/AIDS)1,2. This fungus can infect the brain, causing cryptococcal meningitis, a disease that is fatal if not treated properly. In recent years, there have been serious concerns about the increasing incidence of cryptococcal meningitis in people with normal immune system function. One of the main virulent factors of C. neoformans is its bulk polysaccharide capsule. It consists mainly of a glucuronoxylomannan (GXM), a minor galactoxylomannan (GalXM) and a mannoprotein. The minor capsular polysaccharide of C. neoformans is of great interest as a promising target for vaccine development.
Methods:
The original regio- and stereospecific methods were applied to perform the synthesis of a series of oligosaccharides related to GalXM, including application of stereodirecting groups and optimized conditions for selective removal of orthogonal protective groups. The spatial structure of the synthesized fragments was established using a combination of theoretical (computational) and experimental (NMR) methods.
Results:
Linear and branched oligosaccharides, related to GalXM, containing none, one and two β-D-galactofuranose residues were synthesized for the first time. For this purpose, we have developed а convenient strategy based on the use of an N-phenyltrifluoroacetimidoyl galactosyl donor carrying four different protecting groups with α-stereodirecting effects necessary for the construction of α-(1→6)-linkages in the main chain3. The target compounds were obtained as aminopropyl glycosides, which allows for their transformation to glycoconjugates required for biochemical studies.
Conclusions:
The described compounds related to C. neoformans galactoxylomannan represent a convenient tool for investigation of the features of antifungal immunity, and could be potentially used for development anti-fungal vaccines.
Conflicts of interest:
The authors declare that they have no conflict of interest in the publication of this article. The authors have no conflicts of interest to report in this work. Abstract was not submitted elsewhere and was first published here.
Funding:
This work was supported by the Russian Science Foundation (grant: 19-73-30017-P).
REFERENCES (3)
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Chen Y, Shi ZW, Strickland AB, Shi M. Cryptococcus neoformans infection in the central nervous system: the battle between host and pathogen. J Fungi (Basel). 2022;8(10):1069. doi:10.3390/jof8101069.
2.
Rajasingham R, Govender NP, Jordan A, et al. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis. 2022;22(12):1748-1755. doi:10.1016/S1473-3099(22)00499-6.
3.
Dorokhova VS, Gerbst AG, Komarova BS, et al. Org Biomol Chem. 2021:19(13):2923–2931. doi:10.1039/D0OB02071K.