| Project/Area Number |
22790116
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Drug development chemistry
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| Research Institution | Showa Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 医薬品化学 / PPAR / X線結晶構造解析 / タンパク質NMR / 脂肪酸 / PPARgamma / X-線結晶構造解析 / 酸化型脂肪酸 / 超長鎖脂肪酸 / ESI-質量分析 |
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| Research Abstract |
To understand interaction of PPARr and fatty acids, We applied several techniques, including organic synthesis, X-ray crystallization, crystallographic analysis, protein NMR spectroscopy and in silico analysis. The results of those experiments will follow
(1) We synthesized very-long-chain polyunsaturated fatty acids and oxidized those derivatives.
(2) We obtained co-crystal of PPARr and synthesized fatty acids and solved those structures, which indicates both 5-oxoTrHA and 6-oxoTHA afforded1,6-conjugate adducts. On the other hand, 6-oxoTHA makes extra cavity in PPARr ligand binding pocket.
(3) ESI experiment indicates that reactivity of conjugate addition depends on positioning of conjugated double bond.
(4) NMR experiment revealed that partial agonist 4-oxoDHA moderately shifted residues on helix12 compare to shift of a full agonist.
(5) Those results were verified using modeling software SYBYL
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