Determination and measurement of unusual metabolites of bile acid multi-conjugates excreted in a patient with Nimann-Pick disease type C1.
| Project/Area Number |
15510182
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Nihon University |
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Principal Investigator |
IIDA Takashi Nihon University, College of Humanities and Sciences, Professor, 文理学部, 教授 (60060125)
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| Co-Investigator(Kenkyū-buntansha) |
YABUTA Rie Nihon University, College of Humanities and Sciences, Assistant, 文理学部, 助手
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | unsaturated bile acid / unusual bile acid conjugate / aminoacylamidation / sulfation / N-acetylglucosamidation / liver disease / tandem mass spectrometry / electrospray ionization mass spectrometry / 異常胆汁酸 / 3β,7β-ジヒドロキシ-5-コレン酸 / 胆汁酸多重抱合体 / 3-スルフェート抱合体 / 7-N-アセチルグルコサミン抱合体 / 24-グリシン抱合体 / 24-タウリン抱合体 / ニーマンーピック病-C1型 / ニーマン-ピック病C型 / 特異的疾患マーカー / 胆汁酸三重抱合体 / スルフェート抱合型胆汁酸 / アミド抱合型胆汁酸 / 胆汁酸N-アセチルグルコサミニド |
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| Research Abstract |
The chemical synthesis of 3β,7β-dihydroxy-5-cholen-24-oic acid triply conjugated by sulfuric acid at C-3,N-acetylglucosamine (GlcNAc) at C-7 and glycine (or taurine) at C-24, which are unusual, major metabolites excreted in urine of a patient with Niemann-Pick diseases type C1,is described. Analogous double-conjugates of 3β-hydroxy-7-oxo-5-cholen-24-oic acid were also prepared. The principal reactions involved were : 1)β-D-N-acetylglueosaminidation at C-7 of methyl 3β-tert-butyldimethylsilyloxy (TBDMSi)-7β-hydroxy-5-cholen-24-oate with 2-acetamido-1α-chloro-1,2-dideoxy-3,4,6-tri-O-acetyl-D-glucopyranose in the presence of CdCO_3 in boiling toluene, 2)sulfation at C-3 of the resulting 3β-TBDMSi-7β-GlcNAc with sulfur trioxide-trimethylamine complex in pyridine, and 3)direct aminoacyl amidation at C-24 of the 3β-sulfo-7β-GlcNAc conjugate with glycine methyl ester hydrochloride (or taurine) using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as a coupling agent in DMF. The structures of the multi-conjugated bile acids were characterized by liquid chromatography-mass spectrometry with electrospray ionization probe under the positive and the negative ionization modes.
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Report
(3 results)
Research Products
(19 results)
