Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"



1.Research Institution Osaka University
 
2.Research Area Life Sciences
 
3.Research Field Structure and Functional Control Mechanism of Biomolecules (Structural Biology and Functional Molecules)
 
4.Term of Project FY 1997 〜 FY 2001
 
5.Project Number 97L00502
 
6.Title of Project Glycobiochemistry − Structure and Functions

7.Project Leader
Name Institution,Department Title of Position
Shoichi Kusumoto Osaka University, Graduate School of Science Professor

8.Core Members

Names Institution,Department Title of Position
Sumihiro Hase Osaka University, Graduate School of Science Professor
Masaki Saito Meiji Pharmaceutical University, Graduate School of Pharmaceutical Sciences Professor

9.Summary of Research Results

Biological functions of sugar chains and glycoconjugates were studied on the basis of their chemical structures and interaction with their specific recognition proteins and/or metabolic enzymes. Improved pyridylamination was successfully applied to high sensitivity detection, isolation and structural determination of free cytosolic oligosaccharides and sugar chains of glycoproteins. The presence of brain-specific sugar chains was thus detected and tissue-specific occurrence of their receptors was observed. Study was also focused on the structure and recognition of bacterial cell surface glycoconjugates which activate the defense system of innate immunity in higher animals. Various structural analogues and isotopically labeled derivatives of lipid A, the active entity of endotoxic lipopolysaccharide, were synthesized, and their three dimensional conformation and supramolecular assembly deduced. The recognition system of lipopolysaccharide was also studied with the aid of synthetic lipid A analogues as homogeneous probes. Interaction of heparin and platelets and activation of the latter were analyzed on the molecular basis: specific key sulfated oligosaccharides were detected in heparin. A protein responsible for heparin binding was detected, isolated, and characterized. Genomic sequence of GM3 synthase (sialyltransferase-1) was determined, expressed in Escherichia coli and other cell lines. Genetic regulation of this enzyme, which produces the first biosynthetic member of ganglioside family, provided important information on the role of sugar chains on glycolipids. Production of an active soluble form of the enzyme initiated the study on its recognition mechanism of substrates.

10.Key Words

(1)sugar chains、(2)glycoproteins、(3)glycolipids
(4)ganglyosides、(5)heparin、(6)lipopolysaccharides
(7)pyridylamination、(8)glycosylation、(9)sialyltransferase


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