Inhibition of a prion conversion by suppressing protein fluctuations using small-molecules
Project/Area Number |
24570180
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biophysics
|
Research Institution | Gifu University |
Principal Investigator |
KAMATARI Yuji O. 岐阜大学, 生命科学総合研究支援センター, 助教 (70342772)
|
Co-Investigator(Kenkyū-buntansha) |
KUWATA Kazuo 岐阜大学, 連合創薬医療情報研究科, 教授 (00170142)
AKASAKA Kazuyuki 近畿大学, 先端技術総合研究所, 教授 (50025368)
ODA Masayuki 京都府立大学, 生命環境科学研究科(系), 准教授 (20318231)
|
Co-Investigator(Renkei-kenkyūsha) |
ISHIKAWA Takeshi 長崎大学, 医歯薬学総合研究科, 准教授 (80505909)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | プリオン蛋白質 / プリオン病 / 抗プリオン化合物 / 創薬 / 揺らぎ / 高圧 / 準安定状態 / 抗体 |
Outline of Final Research Achievements |
Prion diseases are fatal neurodegenerative diseases, with no effective treatment. In this study, we firstly categories antiprion compounds and showed some compounds stabilized the native conformation. We then identified fluctuations in prion protein important for its conformational conversion using NMR spectroscopy. We also found new anti-prion compounds including RNA aptamer and tacrolimus. We lastly reviewed importance of cavities for protein function and evolution. This study indicated suppression of conformational fluctuations may be a useful strategy for drug development of neurodegenerative diseases. This study also indicated that a wide range of conformational space needed to be explored.
|
Report
(4 results)
Research Products
(87 results)
-
-
-
-
-
[Journal Article] Identification and characterization of a multispecific monoclonal antibody G2 against chicken prion protein2014
Author(s)
Kamatari, Y. O., Ohta, S., Inoshima, Y., Oda, M., Maruno, T., Kobayashi, Y., Ishiguro, N.
-
Journal Title
Protein Science
Volume: 23
Issue: 8
Pages: 1050-1059
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
-
[Journal Article] FK506reduces abnormal prion protein through the activation of autolysosomal degradation and prolongs survival in prion-infected mice.2013
Author(s)
Nakagaki T, Satoh K, Ishibashi D, Fuse T, Sano K, Kamatari YO, Kuwata K, Shigematsu K, Iwamaru Y, Takenouchi T, Kitani H, Nishida N, Atarashi R.
-
Journal Title
Autophagy.
Volume: 9
Issue: 9
Pages: 1386-1394
DOI
NAID
Related Report
Peer Reviewed
-
[Journal Article] Synthesis of an 11C-Labeled Antiprion GN8 Derivative and Evaluation of Its Brain Uptake by Positron Emission Tomography2013
Author(s)
Tsutomu Kimura, Takeo Sako, Siqin, Junji Hosokawa-Muto, Yi Long Cui, Yasuhiro Wada, Yosky Kataoka, Hisashi Doi, Suehiro Sakaguchi, Masaaki Suzuki, Yasuyoshi Watanabe, Kazuo Kuwata
-
Journal Title
ChemMedChem
Volume: 8(7)
Issue: 7
Pages: 1035-1039
DOI
Related Report
Peer Reviewed
-
[Journal Article] Synthesis and structure-activity relationship of 2-phenyliminochromene derivatives as inhibitors for AKR1B102013
Author(s)
Satoshi Endo, Dawei HU, Miho Suyama, Toshiyuki Matsunaga, Kenji Sugimoto, Yuji Matsuya, Ossama El-Kabbani, Kazuo Kuwata, Akira Hara, Yukio Kitade, Naoki Toyooka
-
Journal Title
Bioorganic & Medicinal Chemistry
Volume: 21(21)
Issue: 21
Pages: 6378-6384
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
[Journal Article] Anti-prion activity of an RNA aptamer and its structural basis2013
Author(s)
Mashima, T., Nishikawa, F., Kamatari Y. O., Fujiwara, H., Saimura, M., Nagata, T., Kodaki, T., Nishikawa, S., Kuwata, K., Katahira, M.
-
Journal Title
Nucleic Acids Research
Volume: 41
Issue: 2
Pages: 1355-1362
DOI
Related Report
Peer Reviewed
-
-
-
-
-
[Journal Article] Molecular analysis of the binding mode of Toll/interleukin-1 receptor (TIR) domain proteins during TLR2 signaling.2012
Author(s)
Nada M, Ohnishi H, Tochio H, Kato Z, Kimura T, Kubota K, Yamamoto T, Kamatari YO, Tsutsumi N, Shirakawa M, Kondo N.
-
Journal Title
Mol Immunol.
Volume: 52
Issue: 3-4
Pages: 108-116
DOI
Related Report
Peer Reviewed
-
[Journal Article] 高圧蛋白質NMR2012
Author(s)
赤坂一之
-
Journal Title
NMR (Bulletin of the Nuclear Magnetic Resonance Society of Japan)
Volume: 3
Pages: 38-45
Related Report
Peer Reviewed
-
[Journal Article] Direct evidence of generation and accumulation of β-sheet-rich prion protein in ScN2a cells de novo illuminated by human IgG1 antibody recognizing β-form but not α-form of prion protein2012
Author(s)
Toshiya Kubota, Yuta Hamazoe, Shuhei Hashiguchi, Daisuke Ishibashi, Kazuyuki Akasaka, Noriyuki Nishida, Shigeru Katamine, Suehiro Sakaguchi, Ryota Kuroki, Toshihiro Nakashima, Kazuhisa Sugimura.
-
Journal Title
The Journal of biological chemistry
Volume: 287巻
Issue: 17
Pages: 14023-14039
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
[Presentation] 抗体を用いた抗原蛋白質の揺らぎの検出2014
Author(s)
Shohey Shimizu, Yoshito Abe, Yuji O. Kamatari, Tadashi Ueda, Takachika Azuma, Masayuki Oda
Organizer
第52回日本生物物理学会年会
Place of Presentation
札幌
Year and Date
2014-09-26
Related Report
-
[Presentation] 抗体 G2 の複数の抗原を特異的に認識する機構2014
Author(s)
Yuji O. Kamatari, Masayuki Oda, Takahiro Maruno, Shohey Shimizu, Yuji Kobayashi, Naotaka Ishiguro
Organizer
第52回日本生物物理学会年会
Place of Presentation
札幌
Year and Date
2014-09-25
Related Report
-
[Presentation] 新規プリオンアプタマーの探索とその構造研究2014
Author(s)
Tsukasa Mashima, Fumiko Nishikawa, Yuji O. Kamatari, Takashi Nagata, Satoshi Nishikawa, Kazuo Kuwata, Masato Katahira
Organizer
第52回日本生物物理学会年会
Place of Presentation
札幌
Year and Date
2014-09-25
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] FK506 reduces abnormal prion protein through the activation of autolysosomal degradation and prolongs survival in prion-infected mice2013
Author(s)
T. Nakagaki, K. Satoh, D. Ishibashi, T. Fuse, K. Sano, Y. O. Kamatari, K. Kuwata, K. Shigematsu, Y. Iwamaru, T. Takenouchi, H. Kitani, N. Nishida, R. Atarashi
Organizer
Asian Pacific Prion Symposium 2013 in Nagasaki
Place of Presentation
長崎
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-