Royal Society of Chemistry, MedChemComm, 10(6), p. 1755-1760, 2015
DOI: 10.1039/c5md00133a
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Mannosylation facilitates the uptake and the internalization of immunogenic peptides by antigen-processing cells expressing mannose receptors at their surface, such as DC-SIGN, a lectin that plays a key role in the immune response against different pathogens. This internalization, processing and subsequent MHC presentation may result in a strong T-cell stimulation. Here, we hypothesized that combining mannose glycodendrons with multivalent presentation of peptide epitopes in likewise dendron format would yield hybrid constructs, named glycodendropeptides (GDPs), with the capacity to enhance peptide immunogenicity, hence providing a novel and versatile platform for applications in immunotherapy. Thus, GDPs of different valencies displaying the NP366-374 epitope, a conserved sequence from the influenza A virus nucleoprotein (NP), have been built by two click chemistry-based methodologies and assessed as potential flu vaccine candidates. Preliminary evaluation of the ability of these constructs to stimulate dendritic cell maturation and lymphocyte proliferation was promising, showing the highest-functionalized NP366-374 GDPs as inducing the strongest immunostimulatory effect.