Synthesis of LacdiNAc-terminated glycoconjugates by mutant galactosyltransferase - A way to new glycodrugs and materials (Retracted Article)
Synthesis of LacdiNAc-terminated glycoconjugates by mutant galactosyltransferase - A way to new glycodrugs and materials (Retracted Article)
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DOI：
10.1093/glycob/cwp010
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发表时间：
2009-05-01
期刊：
影响因子：
4.3
通讯作者：
Kren, Vladimir
中科院分区：
文献类型：
--
作者：
Bojarova, Pavla;Krenek, Karel;Kren, Vladimir
人胎盘β 1,4-半乳糖转移酶i （EC 2.4.1.38）在体内将半乳糖部分从UDP-Gal转移到各种GlcNAc或Glc受体。在这里，我们将其Y284L突变体的构建描述为His(6)propeptide-cat beta 4GalT1结构，其中gal转移酶活性完全被取消，而galnac转移酶活性取而代之。我们利用该突变体合成了三种单价和二价LacdiNAc糖仿制品，产量很好。这些化合物被证明是两种自然杀伤细胞激活受体NKR-P1和CD69的强效配体。合成的二价系链双- lacdinac是目前已知的这两种受体的最佳沉淀剂，在开发免疫活性糖药方面具有很大的潜力。
Human placental beta 1,4-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-cat beta 4GalT1 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.