Establishment of artificial ligands technology for peptide hormone receptors with functional mutations
| Project/Area Number |
16K08544
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
Sakai Kastuya 金沢大学, がん進展制御研究所, 助教 (10523318)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 受容体 / リガンド / 環状ペプチド / ペプチド / 人工リガンド |
|---|
| Outline of Final Research Achievements |
Artificial ligands for growth factor receptors are clinically applicable. We here tried identification of artificial ligands for insulin receptor (IR) using macrocyclic peptide screening, and characterized MET-agonist macrocyclic peptides to establish artificial ligand technology based on macrocyclic peptide. Expression and purification of IR protein with its kinase activity was difficult. Now, purification of IR in nanodiscs is being investigated. We have proved that 1) artificial ligands based on macrocyclic peptide are able to have similar activity compared to natural ligands, 2) partial agonists based on macrocyclic peptide are able to induced biased or selective cellular responses compared to natural ligands, and 3) macrocyclic peptides interact with thier target protein in an unique manner. These results illustrate potential of artificial ligands based on macrocyclic peptides.
|
| Academic Significance and Societal Importance of the Research Achievements |
ペプチド・タンパク質ホルモンや/増殖因子は細胞膜受容体を介して生理活性を発揮する。本課題により低分子人工ペプチド性リガンドを着実に創製できる技術を実証したこと、これらの技術の基盤となる知見を得られたことは、医薬品として際立った薬効をもつ複数の低分子生理活性医薬を創製する技術原理を確立することにつながる。
|
Report
(4 results)
Research Products
(13 results)
-
[Journal Article] Macrocyclic peptide-based inhibition and imaging of hepatocyte growth factor2019
Author(s)
Katsuya Sakai, Toby Passioura, Hiroki Sato, Kenichiro Ito, Hiroki Furuhashi, Masataka Umitsu, Junichi Takagi, Yukinari Kato, Hidefumi Mukai, Shota Warashina, Maki Zouda, Yasuyoshi Watanabe, Seiji Yano, Mikihiro Shibata, Hiroaki Suga, and Kunio Matsumoto
-
Journal Title
Nature Chemical Biology
Volume: 印刷中
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
