2000 Fiscal Year Final Research Report Summary
Development of pseudo-LOS vaccines
| Project/Area Number |
10306022
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | TOTTORI UNIVERSITY |
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Principal Investigator |
RYOHEI Yamasaki Tottori University, Dept of Biochemistry & Biotechnology, Professor, 農学部, 教授 (80273887)
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| Co-Investigator(Kenkyū-buntansha) |
TSUYOSHI Sanekata Tottori University, School of Agriculture, Associate Professor, 農学部, 助教授 (20205991)
KEN Nouda Tottori University, School of Agriculture, Associate Professor, 農学部, 助教授 (60218287)
JUNICHI Tamura Tottori University, School of Education & Regional Sciences, Associate Professor, 教育地域科学部, 助教授 (30221401)
HIROYUKI Koshino Institute for Physical and Chemical Research, Division of Analysis of Molecular Structures, Senior Researcher, 分子構造解析室, 室長 (50321758)
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| Project Period (FY) |
1998 – 2000
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| Keywords | LPS / Lipooligosaccharide (LOS / Neisseria gonorrhoeae / Vaccine / Oligosaccharide |
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| Research Abstract |
1) Determination of MAb 2C7-defined epitope and structural requirements for its epitope expression.
We found that the major LOS produced by strain WG is an elongated form of 15253 LOS ; a lactoneotetraose is linked to the Hep[1] and a lactose to the Hep[2], GlcNAc-(lactose)Hep[2]-(lactoneotetraose)Hep[1] and that 2) the minor LOS component is a N-acetylgalactosaminylated form of the major LOS component. Immunochemical analyses showed that the entire 15253 OS structure, GlcNAc-(lactose)Hep[2]-(lactose)Hep[1], is essential for expression of the 2C7 epitope. Also, some fatty acids in the lipid A moiety are important for the maximum expression of the epitope. In addition, we also disclosed that human sera contain an anti-LOS antibody whose specificity is similar to MAb 2C7. Our study shows that an epitope located close to the inner core could be potentially used as a safe and protective vaccine against N.gonorrhoeae.
2) Synthesis of the 15253 OS
We developed a new method to synthesize L-glycero-D-mannoheptoside in a semi-preparative scale (〜50g). We also synthesized heptoside derivatives which can be used as a donor or an acceptor. By using those derivatives, we found optimal conditions for glycosidation reactions to synthesize partial 15253 OS structures containing branched Hep structures. By synthesizing building blocks for the 15253 OS structure, we developed a strategy for the synthesis of the entire 15253 OS structure.
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