| KOVALOVÁ, Anna, Miroslav LEDVINA, David ŠAMAN, Daniel ZYKA, Monika KUBÍČKOVÁ, Lukáš ŽÍDEK, Vladimír SKLENÁŘ, Petr POMPACH, Daniel KAVAN, Jan BILÝ, Ondřej VANĚK, Zuzana KUBÍNKOVÁ, Markéta VANČUROVÁ, Mária ANTOLÍKOVÁ, Zuzana LEJSKOVÁ, Hynek MRÁZEK, Daniel ROZBESKÝ, Kateřina HOFBAUEROVÁ, Vladimír KŘEN a Karel BEZOUŠKA. Synthetic N-acetylglucosamine based fully branched tetrasaccharide, a mimetic of the endogenous ligand for CD69, activates CD69+ NK cells and killer lymphocytes upon dimerization via a hydrophilic flexible linker. Journal of Medicinal Chemistry. USA: American Chemical Society, 2010, roč. 53, č. 10, s. 4050-4065. ISSN 0022-2623. |
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@article{885814,
author = {Kovalová, Anna and Ledvina, Miroslav and Šaman, David and Zyka, Daniel and Kubíčková, Monika and Žídek, Lukáš and Sklenář, Vladimír and Pompach, Petr and Kavan, Daniel and Bilý, Jan and Vaněk, Ondřej and Kubínková, Zuzana and Vančurová, Markéta and Antolíková, Mária and Lejsková, Zuzana and Mrázek, Hynek and Rozbeský, Daniel and Hofbauerová, Kateřina and Křen, Vladimír and Bezouška, Karel},
article_location = {USA},
article_number = {10},
keywords = {Lymphocyte activation; receptors for carbohydrates; crosslinking; natural killer cells; tumor immunotherapies},
language = {eng},
issn = {0022-2623},
journal = {Journal of Medicinal Chemistry},
title = {Synthetic N-acetylglucosamine based fully branched tetrasaccharide, a mimetic of the endogenous ligand for CD69, activates CD69+ NK cells and killer lymphocytes upon dimerization via a hydrophilic flexible linker},
volume = {53},
year = {2010}
}
TY - JOUR
ID - 885814
AU - Kovalová, Anna - Ledvina, Miroslav - Šaman, David - Zyka, Daniel - Kubíčková, Monika - Žídek, Lukáš - Sklenář, Vladimír - Pompach, Petr - Kavan, Daniel - Bilý, Jan - Vaněk, Ondřej - Kubínková, Zuzana - Vančurová, Markéta - Antolíková, Mária - Lejsková, Zuzana - Mrázek, Hynek - Rozbeský, Daniel - Hofbauerová, Kateřina - Křen, Vladimír - Bezouška, Karel
PY - 2010
TI - Synthetic N-acetylglucosamine based fully branched tetrasaccharide, a mimetic of the endogenous ligand for CD69, activates CD69+ NK cells and killer lymphocytes upon dimerization via a hydrophilic flexible linker
JF - Journal of Medicinal Chemistry
VL - 53
IS - 10
SP - 4050-4065
EP - 4050-4065
PB - American Chemical Society
SN - 00222623
KW - Lymphocyte activation
KW - receptors for carbohydrates
KW - crosslinking
KW - natural killer cells
KW - tumor immunotherapies
N2 - Based on the highly branched ovomucoid-type undecasaccharide that has been shown previously to constitute a physiological ligand for CD69 leukocyte receptor, a systematic investigation of smaller oligosaccharide mimetics has been performed based on the linear and branched N-acetylhexosamine homooligomers prepared synthetically using hitherto unexplored reaction schemes. The systematic structure activity studies revealed the tetrasaccharide GlcNAcb1-3(GlcNAcb1-4)(GlcNAcb1-6)GlcNAc (compound 52) and its a-benzyl-derivative 49 as the best ligand for CD69 with IC50 as high as 10-9 M, thus approaching the affinity of the classical high-affinity ligand GlcNAc17BSA. Compound 68, GlcNAc tetrasaccharide dimerized through a hydrophilic flexible linker, turned out to be effective in activation of CD69+ lymphocytes. It also proved efficient in enhancing natural killing in vitro, decreasing the growth of tumors in vivo, and activating the CD69+ tumor infiltrating lymphocytes examined ex vivo. This compound thus represents a candidate for carbohydrate-based immunomodulators with a promising antitumor potential.
ER -
KOVALOVÁ, Anna, Miroslav LEDVINA, David ŠAMAN, Daniel ZYKA, Monika KUBÍČKOVÁ, Lukáš ŽÍDEK, Vladimír SKLENÁŘ, Petr POMPACH, Daniel KAVAN, Jan BILÝ, Ondřej VANĚK, Zuzana KUBÍNKOVÁ, Markéta VANČUROVÁ, Mária ANTOLÍKOVÁ, Zuzana LEJSKOVÁ, Hynek MRÁZEK, Daniel ROZBESKÝ, Kateřina HOFBAUEROVÁ, Vladimír KŘEN a Karel BEZOUŠKA. Synthetic N-acetylglucosamine based fully branched tetrasaccharide, a mimetic of the endogenous ligand for CD69, activates CD69+ NK cells and killer lymphocytes upon dimerization via a hydrophilic flexible linker. \textit{Journal of Medicinal Chemistry}. USA: American Chemical Society, 2010, roč.~53, č.~10, s.~4050-4065. ISSN~0022-2623.
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