Synthesis of LacdiNAc-terminated glycoconjugates by mutant galactosyltransferase--a way to new glycodrugs and materials.
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.
Bojarová
Pavla
P
Institute of Microbiology, Center for Biocatalysis and Biotransformation, Academy of Sciences of the Czech Republic, Vídenská 1083, 14220 Prague 4, Czech Republic.
Krenek
Karel
K
Wetjen
Katharina
K
Adamiak
Kathrin
K
Pelantová
Helena
H
Bezouska
Karel
K
Elling
Lothar
L
Kren
Vladimír
V
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D016123:Campylobacter jejuni / Q000201:enzymology; D002238:Carbohydrate Epimerases / Q000378:metabolism; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D006001:Glycoconjugates / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000138:chemical synthesis / Q000378:metabolism; D037181:Lectins, C-Type; D009154:Mutation; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013379:Substrate Specificity; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001426:Bacterial Proteins; D002238:Carbohydrate Epimerases; D005700:Galactosyltransferases; D006001:Glycoconjugates; D007785:Lactose; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D000099192:CD69 Antigens; C093701:N-acetylgalactosaminyl-1-4-N-acetylglucosamine; C493310:beta1,4-galactosyltransferase, human; C023223:UDP-N-acetylglucosamine 4-epimerase