Abstract
Human placental beta1,4-galactosyltransferase-I (EC 2.4.1.38) transfers the galactosyl moiety from UDP-Gal to various GlcNAc or Glc acceptors in vivo. Here, we describe the construction of its Y284L mutant as a His(6)propeptide-catbeta4GalT1 construct, in which the Gal-transferase activity was totally abolished in favor of its GalNAc-transferase activity. We used this mutant in the synthesis of three mono- and bivalent LacdiNAc glycomimetics with good yields. These compounds proved to be powerful ligands of two activation receptors of natural killer cells, NKR-P1 and CD69. A synthetic bivalent tethered di-LacdiNAc is the best currently known precipitation agent for both of these receptors and has promising potential for the development of immunoactive glycodrugs.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Bacterial Proteins / metabolism
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Campylobacter jejuni / enzymology
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Carbohydrate Epimerases / metabolism
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Female
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Galactosyltransferases / genetics
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Galactosyltransferases / metabolism*
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Glycoconjugates / biosynthesis
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Glycoconjugates / chemical synthesis*
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Glycoconjugates / metabolism
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Humans
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Lactose / analogs & derivatives*
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Lactose / biosynthesis
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Lactose / chemical synthesis
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Lactose / metabolism
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Lectins, C-Type
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Mutation
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NK Cell Lectin-Like Receptor Subfamily B / metabolism
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Placenta / enzymology
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Pregnancy
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Substrate Specificity
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Bacterial Proteins
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CD69 antigen
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Glycoconjugates
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Lectins, C-Type
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NK Cell Lectin-Like Receptor Subfamily B
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N-acetylgalactosaminyl-1-4-N-acetylglucosamine
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Galactosyltransferases
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beta1,4-galactosyltransferase, human
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Carbohydrate Epimerases
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UDP-N-acetylglucosamine 4-epimerase
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Lactose