Document Detail


Efficient transfer of sialo-oligosaccharide onto proteins by combined use of a glycosynthase-like mutant of Mucor hiemalis endoglycosidase and synthetic sialo-complex-type sugar oxazoline.
MedLine Citation:
PMID:  20647032     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: An efficient method for synthesizing homogenous glycoproteins is essential for elucidating the structural and functional roles of glycans of glycoproteins. We have focused on the transglycosylation activity of endo-ß-N-acetylglucosaminidase from Mucor hiemalis (Endo-M) as a tool for glycoconjugate syntheses, since it can transfer en bloc the oligosaccharide of not only high-mannose type but also complex-type N-glycan onto various acceptors having an N-acetylglucosamine residue. However, there are two major bottlenecks for its practical application: the low yield of the transglycosylation product and the difficulty to obtain the activated sugar oxazoline substrate, especially the sialo-complex type one. METHODS: We carried out the transglycosylation using a glycosynthase-like N175Q mutant of Endo-M, which was found to possess enhanced transglycosylation activity with sugar oxazoline as a donor substrate, in combination with an easy preparation of the sialo-complex-type sugar oxazoline from natural sialoglycopeptide in egg yolk. RESULTS: Endo-M-N175Q showed efficient transglycosylation toward sialo-complex-type sugar oxazoline onto bioactive peptides and bovine ribonuclease B, and each sialylated compound was obtained in significantly high yield. CONCLUSIONS: Highly efficient and simple chemo-enzymatic syntheses of various sialylated compounds were enabled, by a combination of a simple synthesis of sialo-complex-type sugar oxazoline and the Endo-M-N175Q catalyzed transglycosylation. GENERAL SIGNIFICANCE: Our method would be very useful for a practical synthesis of biologically important glycopeptides and glycoproteins.
Authors:
Midori Umekawa; Takayuki Higashiyama; Yurie Koga; Tomonari Tanaka; Masato Noguchi; Atsushi Kobayashi; Shin-Ichiro Shoda; Wei Huang; Lai-Xi Wang; Hisashi Ashida; Kenji Yamamoto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-18
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1800     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-11-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1203-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Graduate School of Biostudies, Kyoto University, Kyoto, Japan. mumekawa@umich.edu
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MeSH Terms
Descriptor/Qualifier:
Carbohydrate Conformation
Carbohydrate Sequence
Glycopeptides / metabolism
Glycosylation
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / genetics*,  metabolism*
Molecular Sequence Data
Mucor / enzymology*,  genetics
Mutation / genetics*
Oligosaccharides / metabolism*
Oxazoles / isolation & purification,  metabolism*
Sialic Acids / metabolism*
Chemical
Reg. No./Substance:
0/Glycopeptides; 0/Oligosaccharides; 0/Oxazoles; 0/Sialic Acids; EC 3.2.1.96/Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase

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