Design of highly selective MMP inhibitors by coupling selective peptide inhibitors with physiological MMP-binding proteins
Project/Area Number |
25440033
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Structural biochemistry
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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.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Small-molecule auxin inhibitors that target YUCCA are powerful tools for studying auxin function.2015
Author(s)
Kakei Y, Yamazaki C, Suzuki M, Nakamura A, Sato A, Ishida Y, Kikuchi R, Higashi S, Kokudo Y, Ishii T, Soeno K, Shimada Y
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Journal Title
Plant J
Volume: 84
Issue: 4
Pages: 827-37
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Amino-terminal fragments of laminin γ2 chain stimulate migration of metastatic breast cancer cells by interacting with CD442015
Author(s)
Sato, H, Oyanagi, J., Komiya, E., Ogawa, T, Higashi, S., Miyazaki, K.
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Journal Title
Clin. Exp. Metastasis
Volume: 32
Issue: 5
Pages: 405-415
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Angiomodulin (AGM/IGFBP-rP1) is a molecular marker of vascular endothelial cells activated by VEGF in human breast cancers.2014
Author(s)
Komiya, E, Sato, H., Ise, I., Watanabe, N., Higashi, H., Miyagi, Y., Miyazaki, K.
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Journal Title
Cancer Med
Volume: 印刷中
Issue: 3
Pages: 537-549
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of transforming growth factor-β signaling potentiates tumor cell invasion into collagen matrix induced by fibroblast-derived hepatocyte growth factor.2014
Author(s)
Oyanagi, J., Kojima, N., Sato, H., Higashi, S., Kikuchi, K., Sakai, K., Matsumoto, K., Miyazaki, K.
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Journal Title
Exp Cell Res.
Volume: 印刷中
Issue: 2
Pages: 267-279
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Amino-terminal fragments of laminin gamma2 chain retract vascular endothelial cells and increase vascular permeability.2014
Author(s)
Sato, H, Oyanagi, J., Komiya, E., Ogawa, T, Higashi, S., Miyazaki, K.
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Journal Title
Cancer Sci.
Volume: 105
Issue: 2
Pages: 168-175
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Modulation of matrix metalloproteinase-9 secretion from tumor-associated macrophage-like cells by proteolytically processed laminin-332 (laminin-5).2014
Author(s)
Kamoshida, G., Ogawa, T., Oyanagi, J., Sato, H., Komiya, E., Higashi, S., Miyazaki, K., Tsuji, T.
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Journal Title
Clin. Exp. Metastasis
Volume: 31
Issue: 3
Pages: 285-291
DOI
Related Report
Peer Reviewed
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