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

Varování

Publikace nespadá pod Filozofickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
Autoři

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

Rok publikování 2010
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Medicinal Chemistry
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Biochemie
Klíčová slova Lymphocyte activation; receptors for carbohydrates; crosslinking; natural killer cells; tumor immunotherapies
Popis 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.
Související projekty:

Používáte starou verzi internetového prohlížeče. Doporučujeme aktualizovat Váš prohlížeč na nejnovější verzi.