Biomedical Engineering Reference
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crucial to ensure a safe delivery of the multiantigenic vaccine to the antigen
presenting cells (APC) and the further internalization and antigen processing
resulting in the activation of the immune response. It should also be mentioned
that another additional approach for antigen delivery would consist in using,
instead of carbohydrate antigens, a polymannosyl cluster that efficiently targets
mannose receptors expressed on the surface of APC but this strategy won't be
discussed in this chapter (for significant examples, see references [14-15]). To
date, several molecular constructions combining a T-cell immunostimulant
peptide epitope and TACAs have been developed on the basis of various low
molecular weight scaffolds with accurate chemical definition such as linear
peptides and dendrimer like structures (Figure 2, strategy B). The following parts
of this chapter focus on the synthesis of these different classes of glycopeptides
that are currently used either for coupling to a protein carrier or as full synthetic
vaccine candidate.
Strategy A
Strategy B
Carbohydrate
marker (TACA)
Peptide dendrimer
Linear peptide
Cyclopeptide
= carrier protein, lipid or
nanoparticule
= Immunostimulant peptide
Fig. 2. Representation of the two main approaches for the design of synthetic vaccines.
3. Synthesis of Linear Glycopeptide-based Conjugates and Linkers
Glycopeptide and neoglycopeptide synthesis is an extremely vast topic as shown
by the large number of related reviews (for excellent reviews, see [16-17]).
Whereas the elongation of orthogonally protected peptidic structures by standard
solid phase strategy rarely presents synthetic difficulties, the synthesis of
complex carbohydrate structures, for which extraction from natural sources is not
providing enough material for the construction of homogeneous glycoconjugates,
reveals however more tedious. Although spectacular progress has been made in
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