| Project/Area Number |
25440033
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Structural biochemistry
|
|---|
| Research Institution | Yokohama City University |
|---|
Principal Investigator |
Higashi Shouichi 横浜市立大学, 生命ナノシステム科学研究科, 教授 (10275076)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
SATO MAMORU 横浜市立大学, 生命医科学研究科, 教授 (60170784)
HASHIMOTO HIROSHI 静岡県立大学, 薬学部, 教授 (40336590)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | matrix metalloproteinase / selective inhibitor / APP-IP / MMP-7 / MMP-9 / TIMP-1 / HAI-1 / 細胞間接着 / マトリックスメタロプロテアーゼ / MMP / TIMP / がん転移 / 高特異性インヒビター / ペプチドインヒビター / MMP-2 / MT1-MMP |
|---|
| Outline of Final Research Achievements |
(1) We developed peptide inhibitors with enhanced selectivity toward MMP-7, MMP-9 and MMP-14, respectively, by modifying the amino acid sequence of APP-IP, an MMP-2-selective decapeptide inhibitor. (2) We further designed a highly selective and strong protein inhibitor against MMP-9 and MMP-2 by combining the variant of APP-IP with enhanced MMP-9 selectivity and TIMP-1, which binds specifically to the non-catalytic domains of MMP-9 and MMP-2. (3) We identified hepatocyte growth factor activator inhibitor type I (HAI-1), a type I membrane protein, as a specific substrate of MMP-7 on cancer cell surface, and found that the extracellular domain of HAI-1 released by the MMP-7-catalyzed cleavage acts as a cell-adhesion protein.
|
