Synthesis of Multivalent Glycoconjugates Containing the Immunoactive LELTE Peptide: Effect of Glycosylation on Cellular Activation and Natural Killing by Human Peripheral Blood Mononuclear Cells.

Pentapeptide diacidic sequence LELTE, derived from the mycobacterial heat shock protein hsp65, has been recently identified as a "danger" signal of the immune system effective via specific binding to the universal leukocyte triggering receptor CD69. This sequence is not active per se, only after its presentation within the multivalent environment of its parent protein, or after artificial dimerization using a std. bifunctional reagents. Here, the authors describe an entirely new way of presenting of this peptide based on its attachment to a cyclopeptide RAFT scaffold (K-K-K-P-G)2 through the $ε$-amino group of lysine residues, alone or in combination with the carbohydrate epitope $\alpha$GalNAc. The ability of such RAFT scaffolds to ppt. the target CD69 receptor or to activate CD69-pos. cells is enhanced in compds. 2 and 4 possessing combined peptide/carbohydrate expression. Compds. 2 and 4 are highly efficient activators of natural killer lymphocytes, but they are completely inactive from the point of view of activation-induced apoptosis of lymphocytes by the target cells. These unique properties make the combined peptide/carbohydrate RAFTs highly suitable for future evaluation in animal tumor therapies in vivo and predict them to be readily available and efficient immunoactivators. [on SciFinder(R)]

Références

Titre
Synthesis of Multivalent Glycoconjugates Containing the Immunoactive LELTE Peptide: Effect of Glycosylation on Cellular Activation and Natural Killing by Human Peripheral Blood Mononuclear Cells.
Type de publication
Article de revue
Année de publication
2010
Revue
J. Am. Chem. Soc.
Volume
132
Pagination
6800–6808
ISSN
0002-7863
Soumis le 12 avril 2018