Document Detail


Chemoenzymatic synthesis of GD3 oligosaccharides and other disialyl glycans containing natural and non-natural sialic acids.
MedLine Citation:
PMID:  19947630     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 Siaalpha2-8Sia component with different natural and non-natural sialic acids. In the first step, alpha2-3- or alpha2-6-linked monosialylated oligosaccharides were obtained using a one-pot three-enzyme approach. These compounds were then used as acceptors for the alpha2-8-sialyltransferase activity of a recombinant truncated multifunctional Campylobacter jejuni sialyltransferase CstII mutant, CstIIDelta32(I53S), to produce disialyl oligosaccharides. The alpha2-8-sialyltransferase activity of CstIIDelta32(I53S) 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.
Authors:
Hai Yu; Jiansong Cheng; Li Ding; Zahra Khedri; Yi Chen; Sharlene Chin; Kam Lau; Vinod Kumar Tiwari; Xi Chen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  131     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-23     Completed Date:  2010-03-02     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18467-77     Citation Subset:  IM    
Affiliation:
Department of Chemistry, University of California-Davis, One Shields Avenue, Davis, California 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Campylobacter jejuni / enzymology
Gangliosides / chemical synthesis*
Oligosaccharides / chemical synthesis
Polysaccharides / chemical synthesis*
Sialic Acids / chemistry*
Sialyltransferases / metabolism*
Substrate Specificity
Grant Support
ID/Acronym/Agency:
R01 GM076360-04/GM/NIGMS NIH HHS; R01GM076360/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Gangliosides; 0/Oligosaccharides; 0/Polysaccharides; 0/Sialic Acids; 62010-37-1/ganglioside, GD3; EC 2.4.99.-/Sialyltransferases

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