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3-Aminopropyl α-(1→3)-pentaglucoside, a fragment of α-(1→3)-glucan of the cell wall of Aspergillus fumigatus, has been synthesized in a blockwise approach. The application of mono- and disaccharide N-phenyltrifluoroacetimidates bearing a stereodirecting 6-O-benzoyl group was essential for stereoselective α-glucosylations. In the products, p-methoxyphenyl and levulinoyl groups served as orthogonal protecting groups for the anomeric position and 3-OH group, respectively. Their removal from shared blocks led to donors and acceptors that were used for the synthesis of pentasaccharides. Coupling of free α-(1→3)-pentaglucoside with biotin and bovine serum albumin (BSA) gave glycoconjugate tools for mycological studies. Immunization of mice with the BSA conjugate induced the generation of antibodies that recognize α-(1→3)-glucan on A. fumigatus cell wall and distinguish its morphotypes. This discovery represents a first step to the development of a diagnostic test system and a vaccine to detect and fight this life-threatening pathogen.

Biotinylated hepta-, nona- and undeca-α-(1 → 3)-d-glucosides representing long oligosaccharides of α-(1 → 3)-d-glucan, one of the major components of the cell walls of the fungal pathogen Aspergillus fumigatus, were synthesized for the first time via a blockwise strategy. Convergent assembly of the α-(1 → 3)-d-glucan chains was achieved by glycosylation with oligoglucoside derivatives bearing 6-O-benzoyl groups. Those groups are capable of remote α-stereocontrolling participation, making them efficient α-directing tools even in the case of large glycosyl donors. Synthetic biotinylated oligoglucosides (and biotinylated derivatives of previously synthesized tri- and penta-α-(1 → 3)-d-glucosides) loaded on streptavidin microtiter plates were shown to be better recognized by anti-α-(1 → 3)-glucan human polyclonal antibodies and to induce higher cytokine responses upon stimulation of human peripheral blood mononuclear cells than their natural counterpart, α-(1 → 3)-d-glucan, immobilized on a conventional microtiter plate. Attachment of the synthetic oligosaccharides equipped with a hydrophilic spacer via the streptavidin–biotin pair allows better spatial presentation and control of the loading compared to the random sorption of natural α-(1 → 3)-glucan. Increase of oligoglucoside length results in their better recognition and enhancement of cytokine production. Thus, using synthetic α-(1 → 3)-glucan oligosaccharides, we developed an assay for the host immune response that is more sensitive than the assay based on native α-(1 → 3)-glucan.

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Who designed the cover?The cover-page was conceptualized by Nikolay. Bohzena, Maria and Vishukumar contributed mainly to the design and production of the cover. Jean-Paul provided the beautiful microphotograph of A. fumigatus.What is the most significant result of this study?Development of an approach to the synthesis of long enough a-(1!3)-linked glucose oligomers. Despite the tremendous progress in glycosylation methodology during past decades, highly stereoselective preparation of a-glycosides is still a challenge. The stereoselectivity of glycosylation is especially important, when the target molecule contains many a-linkages. Our approach is based on the ability of remote O-acyl protecting groups in certain positions of the pyranose cycle to govern stereochemistry of the glycoside bond formation. Not less significant is the application of the pentasaccharide for studying the fungal cell wall. What aspects of this project do you find most exciting?Collaboration between chemists and mycologists: Chemists can synthesize very complex molecules, and the successful completion of a multistep synthesis is exciting in itself. But much more exciting is the knowledge of the fact that the prepared compound is not simply put on the shelf or in the freezer but may provide new opportunities for investigators from other scientific fields. This is just the case in our research. The group of carbohydrate chemists from Moscow has synthesized a-(1!3)-pentaglucoside conjugated with protein, while mycologists from Paris have shown that these compounds are useful tools to study the A. fumigatus cell wall. Our collaboration is in the very beginning and we hope it will bring more exciting results. What future opportunities do you see?The longer oligomeric glucoside conjugates, which are now under preparation, may be a basis for designing vaccines against A. fumigatus (the most ubiquitous airborne fungal pathogen) and the monoclonal antibodies developed against them. The synthesis and evaluation of antimicrobial conjugated carbohydrate vaccines is being actively developed now in many research centers all over the world, and we hope we may contribute to solving the problem of prevention and treatment of fungal infections.Invited for the cover of this issue is the group of researchers from N.D. Zelinsky Institute of the Russian Academy of Sciences and the Pasteur Institute, Paris. The coverpicture illustrates our research: the production of antibodies against Aspergillus fumigatus cell wall a-(1!3)-glucan using chemically prepared pentasaccharide fragment of a-(1!3)-glucan conjugated with a carrier protein. Read the full text of the article at