| Co-Investigator(Kenkyū-buntansha) |
KATSURAYA Kaname University of Tokyo, Institute of Industrial Science, Research Associate, 生産技術研究所, 助手 (20251465)
KATO Takash University of Tokyo, Institute of Industrial Science, Associate Professor, 生産技術研究所, 助教授 (70214377)
SHOJI Tadao Dainippon Ink and Chemicals Inc., Central Research Laboratories, Group Leader, グループリーダー
KUZUHARA Hiroyoshi Saitama University, Faculty of Engineering, Professor, 工学部, 教授 (50100053)
NAKASHIMA Hideki Yamanashi Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (20192669)
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| Research Abstract |
Starting from oligosaccharides, sulfated alkyl oligosaccharides with high anti-AIDS virus (HIV) activity in vitro were synthesized. The key reaction affording the sulfated alkyl oligosaccharide was the binding of a long alkyl group to reducing end of an oligosaccharide.
Difficulties in separation and purification which were inherent in the medium molecular weight compounds were mostly solved by use of high performance and column chromatographies in addition to an elaborated desalting process.
As a result, the target compound with a high activity was obtained. Effects of the structure and residue number of both oligosaccharides and alkyl groups were examined.
Thereby, starting both from laminari oligosaccharides (abbreviated as L) having 5 to 9 glucose residues and from malto oligosaccharides (M) having 4 to 7 glucose residues, sulfated alkyl oligosaccharides such as sulfated dodecyl laminari-pentaosides (abbreviated as SL5-C12), SL5-C18, SL9-C12, SL9-C18, SM4-C12, SM5-C12, SM7-C12, SM7-C18 and so on, were synthesized. Furthermore, branched alkyls, chiral alkyls, aralkyls, and fluoroalkyls were examined in place of the n-alkyl.
For these various compounds, the anti-HIV activity was measured by means of MT-4 cells and HTLV-_<HIB> viruses. It was concluded that sulfated dodecyl laminaripentaoside which had a very high anti-HIV activity represented by EC_<50> of 0.1mug/mL was an optimum compound. This compound exhibited considerably long harf-life time of about 10 to 20 h, when it was intravenously injected to mice. A large scale production of laminaripentaose was tried by both enzymic degradation and acidic hydrolysis of curdlan, revealing that separation of the compound from the oligosaccharides mixture is able to be performed by long-time chromatography.
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