Bearing in mind the often insufficient metabolic stability of carbohydrate antigens, which impairs both the bioavailability and immunogenicity of a given hapten, the development of chemically modified analogs with improved antigenicity is an important step towards effective glycoconjugate vaccines. Recently, strategic glycan fluorination has become an interesting approach to this, and several examples of fluorinated carbohydrate antigens that show better metabolic stabilities and comparable or even enhanced immunogenicities have been reported to date. In this paper, we present a small library of fluorinated trisaccharides based on a privileged motif from the lipophosphoglycan capping structure of Leishmania donovani, a protozoan parasite responsible for fatal visceral leishmaniasis. These epitope analogs were synthesized by a sequential [1+1+1] glycosylation strategy. An amine linker is present at the reducing end to allow conjugation and enable future applications in immunological studies for the development of diagnostic tools and vaccines.
The decoding of the mechanisms underlying glycan‐mediated recognition in disease and health requires access to structurally well‐defined oligosaccharides as molecular probes. Owing to their often favourable properties, deoxyfluorosugars have emerged as a promising class of selectively modified carbohydrates for biological and immunological studies. In particular the enhanced metabolic stability and intrinsic immunogenicity of fluorinated carbohydrates has spurred research on their use for vaccine design. Herein, a first total synthesis of an orthogonally protected and fluorinated hexasaccharide–threonine conjugate of the natural sialophorin antigen has been accomplished. Starting from readily available monosaccharide building blocks, the targeted glycosyl amino acid 1 was assembled by a [3+3′]‐block glycosylation strategy. Together with its (1→4)‐linked regioisomer the glycan mimic can be applied to solid‐phase glycopeptide synthesis to access novel sialophorin‐derived molecular tools for functional and biomedical studies.
The cover picture shows in the background a snapshot of the beautiful landscape around Wallberg peak in the Mangfall mountain range near Munich (Bavarian Alps). It symbolizes the strenuous efforts required for the synthesis of complex carbohydrate‐based antigens and the journey towards the development of effective glycoconjugate vaccines. The first total synthesis of fluorinated hexasaccharide–threonine conjugates enables antigen mimics of sialophorin glycoprotein fragments to become accessible for biological studies and medicinal applications. Details of the synthetic strategy based on a [3+3']‐block glycosylation approach are discussed in the article by A. Hoffmann‐Röder et al. on http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201600523/abstract.
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