Synthetic N-Acetyl-D-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69+ Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

0343794 - ÚOCHB 2011 RIV US eng J - Journal Article
Kovalová, Anna - Ledvina, Miroslav - Šaman, David - Zyka, Daniel - Kubíčková, M. - Žídek, L. - Sklenář, V. - Pompach, P. - Kavan, D. - Bílý, J. - Vaněk, O. - Kubínková, Z. - Libigerová, M. - Ivanová, L. - Antolíková, M. - Mrázek, H. - Rozbeský, D. - Hofbauerová, Kateřina - Křen, Vladimír - Bezouška, K.
Synthetic N-Acetyl-D-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69+ Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker.
Journal of Medicinal Chemistry. Roč. 53, č. 10 (2010), s. 4050-4065. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA MŠMT 1M0505; GA ČR GA303/09/0477; GA ČR GD305/09/H008; GA ČR GP203/09/P024; GA AV ČR KAN200520703; GA AV ČR KAN200100801
Grant - others:GA MŠk(CZ) LC06030
Program: LC
Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510
Keywords : CD69 * mimetic * tetrasaccharide
Subject RIV: CC - Organic Chemistry
Impact factor: 5.207, year: 2010

The systematic structure-activity studies revealed the fully synthetized tetrasaccharide GlcNAc beta1-3(GlcNAc beta1-4)(GlcNAc beta1-6)GlcNAc and its R-benzyl derivative as the best ligands forCD69 with IC50 as high as 10-9 M. Furthermore, this saccharide dimerized through a hydrophilic flexible linker, turned out to be effective in activating CD69+ lymphocytes. It also proved efficient in enhancing natural killing in vitro, decreasing the growth of tumors in vivo, and activating theCD69+ tumor infiltrating lymphocytes examined ex vivo.
Permanent Link: http://hdl.handle.net/11104/0186184