Development of a new foldamer as a mimetic of alfa-helix
| Project/Area Number |
17K15476
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | ペプチドミメティクス / 配座制御 / フォルダマー / ペプチド |
|---|
| Outline of Final Research Achievements |
I designed of optically active cyclopropane δ-amino acid oligomers wth various stereochemistries and calculated their most stable conformation using MacroModel. As a result, a homo-oligomers of specific stereoisomer of an optically active cyclopropane δ-amino acid form stable, right-handed helix. Then, I synthesized the optically active cyclopropane δ-amino acid monomer from the optically active glycidol via a stereoselective Grignard reaction and an asymmetric alkylation using asymmetric auxiliary groups in 18 steps. After oligomerization to various lengths, CD measurement, NMR measurement, and X-ray crystal structure analysis of the three-dimensional structure were performed. As a result, it was found that a hexameric or higher oligomer forms a helical secondary structure as calculated.
|
| Academic Significance and Societal Importance of the Research Achievements |
タンパク質間相互作用の制御を狙ったペプチドミメティクスの開発研究は盛んになされているものの、普遍的な方法論といえるものが確立されているわけではない。本研究は、様々なタンパク質間相互作用に適用可能な一般性の高い新規ペプチドミメティクス開発方法論を提示・実践するものである。本研究の成果は、タンパク質間相互作用を標的としたペプチドミメティクス創薬の新たな基盤として発展する可能性を秘める。
|
Report
(3 results)
Research Products
(32 results)
-
-
-
-
-
-
-
[Journal Article] Cyclopropane-Based Peptidomimetics Mimicking Wide-Ranging Secondary Structures of Peptides: Conformational Analysis and Their Use in Rational Ligand Optimization.2017
Author(s)
A. Mizuno, T. Kameda, T. Kuwahara, H. Endoh, Y. Ito, S. Yamada, K. Hasegawa, A. Yamano, M. Watanabe, M. Arisawa, S. Shuto
-
Journal Title
Chem. Eur. J.
Volume: 23
Issue: 13
Pages: 3159-3168
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] シクロプロパンの構造特性に基づく膜透過性環状ペプチドの設計と合成2018
Author(s)
植村真衣, 加藤七海,松井耕平, 桑原智希, 渡邉瑞貴, 福田隼, 竹内恒, 広川貴次, 武隈洋, 菅原 満, 周東 智
Organizer
日本薬学会第138年会
Related Report
-
-
-
-
-
-
-
-
