Synthesis of LacdiNAc-terminated glycoconjugates by mutant galactosyltransferase – A way to new glycodrugs and materials
Abstract
Human placental β1,4-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 His6propeptidecatβ4GalT1 construct, in which the Gal-transferase aktivity was totally abolished in favor of its GalNAc-transferase activity.
We used this mutant in the synthesis of three monoand 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.