Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α‐(1→3)‐Glucan and Their Use in the Generation of Antibodies to Trace Aspergillus fumigatus Cell Wall

Abstract

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

A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future

“…Studies found that using biotinylated capsular polysaccharide of S. pneumoniae type IV (b-CPS4) noncovalently bound to Psp/Psa-SA was sufficient to produce a superior humoral and cellular immune response as compared to the protein antigen alone [ 146 , 147 ]. This strategy can be further extended to other antigenic carbohydrates, limited only by the availability or generation of biotinylated species [ 148 , 149 ] in the case of the biotin-SA system. This approach may be generally extendable to other carrier molecules and/or modular binding partners when suitable for development of a particular vaccine.…”