Chemoenzymatic synthesis of GD3 oligosaccharides and other disialyl glycans containing natural and non-natural sialic acids

Hai Yu, Jiansong Cheng, Li Ding, Zahra Khedri, Yi Chen, Sharlene Chin, Kam Lau, Vinod Kumar Tiwari, Xi Chen

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

In order to understand the biological importance of naturally occurring sialic acid variations on disialyl structures in nature, we developed an efficient two-step multienzyme approach for the synthesis of a series of GD3 ganglioside oligosaccharides and other disialyl glycans containing a terminal Siaα2-8Sia component with different natural and non-natural sialic acids. In the first step, α2-3- or α2-6-linked monosialylated oligosaccharides were obtained using a one-pot three-enzyme approach. These compounds were then used as acceptors for the α2-8-sialyltransferase activity of a recombinant truncated multifunctional Campylobacter jejuni sialyltransferase CstII mutant, CstIIΔ32153S, to produce disialyl oligosaccharides. The α2-8-sialyltransferase activity of CstIIΔ32153S has promiscuous donor substrate specificity and can tolerate various substitutions at C-5 or C-9 of the sialic acid in CMP-sialic acid, while its acceptor substrate specificity is relatively restricted. The terminal sialic acid residues in the acceptable monosialylated oligosaccharide acceptors are restricted to Neu5Ac, Neu5Gc, KDN, and some of their C-9-modified forms but not their C-5 derivatives. The disialyl oligosaccharides obtained are valuable probes for their biological studies.

Original languageEnglish (US)
Pages (from-to)18467-18477
Number of pages11
JournalJournal of the American Chemical Society
Volume131
Issue number51
DOIs
StatePublished - Dec 30 2009

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

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