| Project/Area Number |
17K15435
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Ogawa Shoujiro 東京理科大学, 薬学部薬学科, 講師 (30546271)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 誘導体化 / LC/ESI-MS/MS / モノヒドロキシ-7-デヒドロコレステロール / ステロール / Cookson型誘導体化試薬 / 先天性代謝異常症 / Smith-Lemli-Opitz症候群 / ヒドロキシ-7-デヒドロコレステロール / ESI増強誘導体化 / 分析科学 / 先天性コレステロール代謝異常症 / 質量分析計 / 先天性コレステロール生合成不全症 / SLOS / ステロイド / 診断マーカー / 重水素標識 |
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| Outline of Final Research Achievements |
The purpose of this research was to find a novel diagnostic marker for SLOS in choresterol disorder. Furthermore, I have also developed a novel derivatization reagent for increasing assay sensitivity based on LC/ESI-MS/MS analysis. 24S-Hydroxy-7-dehydrocholesterol was synthesized from inexpensive bile acid analogue in more than 10 steps, and 4α- and 4-βhydroxy-7-dehydrocholesterol was obtained from cholesterol in several synthesis steps. Separately, serum of SLOS model rats prepared by ingestion of 7-dehydrocholesterol reductase inhibitor AY9944 was also obtained.
Peaks derived from 4α- and 4-β-hydroxy-7-dehydrocholesterol were clearly observed in the model rat serum as measured by LC/ESI-MS/MS, and these are expected as diagnostic markers for SLOS.
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| Academic Significance and Societal Importance of the Research Achievements |
PAを指標とした誘導体化試薬のデザインを基に，より高い検出感度向上能を有する試薬を開発できたことで，少量の生体試料で臨床診断が可能となった．
また4α-及び4β-OH-7-DHCがSLOSの新規な診断マーカー候補化合物として見出されたことから，我々の誘導体化試薬とLC/ESI-MS/MSを組み合わせたモノヒドロキシ-7-DHCの分析を新生児血清 (あるいはより少量の乾燥露紙血など) 分析に応用すれば，早期の診断法開発への道が開かれるものと期待される．
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