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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F10%3A00044042" target="_blank" >RIV/00216224:14310/10:00044042 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

<a href="/cs/project/LC06030" target="_blank" >LC06030: Biomolekulární centrum</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

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Svazek periodika

53

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

16

Strana od-do

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Kód UT WoS článku

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EID výsledku v databázi Scopus

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