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
Status retracted Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication
PubMed
20433142
DOI
10.1021/jm100055b
Knihovny.cz E-resources
- MeSH
- Acetylglucosamine analogs & derivatives chemical synthesis chemistry pharmacology MeSH
- Lymphocyte Activation MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Killer Cells, Natural drug effects immunology metabolism MeSH
- Antigens, CD metabolism MeSH
- Antigens, Differentiation, T-Lymphocyte metabolism MeSH
- Dimerization MeSH
- Immunologic Factors chemical synthesis chemistry pharmacology MeSH
- Rats MeSH
- NK Cell Lectin-Like Receptor Subfamily B metabolism MeSH
- Lectins, C-Type metabolism MeSH
- Drug Screening Assays, Antitumor MeSH
- Humans MeSH
- Ligands MeSH
- Melanoma, Experimental immunology pathology MeSH
- Molecular Mimicry MeSH
- Models, Molecular MeSH
- Molecular Sequence Data MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Oligosaccharides chemical synthesis chemistry pharmacology MeSH
- Recombinant Proteins chemistry MeSH
- Carbohydrate Sequence MeSH
- In Vitro Techniques MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Retracted Publication MeSH
- Names of Substances
- Acetylglucosamine MeSH
- Antineoplastic Agents MeSH
- Antigens, CD MeSH
- CD69 antigen MeSH Browser
- Antigens, Differentiation, T-Lymphocyte MeSH
- Immunologic Factors MeSH
- NK Cell Lectin-Like Receptor Subfamily B MeSH
- Lectins, C-Type MeSH
- Ligands MeSH
- Oligosaccharides MeSH
- Recombinant Proteins MeSH
On the basis of the highly branched ovomucoid-type undecasaccharide that had been shown previously to be an endogenous ligand for CD69 leukocyte receptor, a systematic investigation of smaller oligosaccharide mimetics was performed based on linear and branched N-acetyl-d-hexosamine homooligomers prepared synthetically using hitherto unexplored reaction schemes. The systematic structure-activity studies revealed the tetrasaccharide GlcNAcbeta1-3(GlcNAcbeta1-4)(GlcNAcbeta1-6)GlcNAc (compound 52) and its alpha-benzyl derivative 49 as the best ligand for CD69 with IC(50) as high as 10(-9) M. This compound thus approaches the affinity of the classical high-affinity neoglycoprotein ligand GlcNAc(23)BSA. Compound 68, GlcNAc tetrasaccharide 52 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 the CD69(+) tumor infiltrating lymphocytes examined ex vivo. This compound is thus a candidate for carbohydrate-based immunomodulators with promising antitumor potential.
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