Development of highly selective inhibitors against individual MMPs
Project/Area Number |
21570118
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Structural biochemistry
|
Research Institution | Yokohama City University |
Principal Investigator |
HIGASHI Shouichi 横浜市立大学, 大学院・生命ナノシステム科学研究科, 准教授 (10275076)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
Keywords | 分子認識及び相互作用 / マトリックスメタロプロテアーゼ / MMP-2 / β-アミロイド前駆体タンパク質 / MMPインヒビター / タンパク質結晶構造解析 / 酵素活性阻害機構 / 高選択性阻害剤 / がんの浸潤・転移 / MMP-7 / コレステロール硫酸 / laminin-332 / fibronectin / 基質特異性変化 / 細胞表層プロテオリシス / 癌の浸潤・転移 / β-アミロイド前駆体タンパク / TIMP-2 / 血小板凝集 / 血栓症 |
Research Abstract |
(1) We determined the crystal structure of the catalytic domain of MMP-2 in complex with decapeptide inhibitor APP-IP, and clarified its mode of the MMP-2-selective inhibition.(2) We designed a highly selective and strong inhibitor against MMP-2 by combining the MMP-2-selective peptide inhibitor APP-IP and physiological MMPs inhibitor TIMP-2.(3) We clarified the mechanism of the cholesterol sulfate-mediated alteration of the substrate preference of MMP-7 ; clarification of the mechanism provides the clue to develop MMP-7-selective inhibitors.
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Report
(4 results)
Research Products
(44 results)