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

0348154 - MBÚ 2011 RIV US eng J - Journal Article
Renaudet, O. - Křenek, Karel - Bossu, I. - Dumy, P. - Kádek, A. - Adámek, David - Vaněk, O. - Kavan, Daniel - Gažák, Radek - Šulc, Miroslav - Bezouška, K. - Křen, Vladimír
Synthesis of Multivalent Glycoconjugates Containing the Immunoactive LELTE Peptide: Effect of Glycosylation on Cellular Activation and Natural Killing by Human Peripheral Blood Mononuclear Cells.
Journal of the American Chemical Society. Roč. 132, č. 19 (2010), s. 6800-6808. ISSN 0002-7863. E-ISSN 1520-5126
R&D Projects: GA MŠMT(CZ) LC06010; GA MŠMT 1M0505; GA AV ČR IAA400200503; GA ČR GA303/09/0477; GA ČR GD305/09/H008
Institutional research plan: CEZ:AV0Z50200510
Keywords : KILLER-CELLS * TN ANTIGEN * RECEPTOR
Subject RIV: EE - Microbiology, Virology
Impact factor: 9.019, year: 2010

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 standard bifunctional reagents. Here we 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 αGalNAc. The ability of such RAFT scaffolds to precipitate the target CD69 receptor or to activate CD69-positive cells is enhanced in compounds 2 and 4 possessing combined peptide/carbohydrate expression. Compounds 2 and 4 are highly efficient activators of natural killer lymphocytes
Permanent Link: http://hdl.handle.net/11104/0188757