Elucidation of the mode of action of aplyronine A using hybrid analog
| Project/Area Number |
18K14343
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | ハイブリッドアナログ / アプリロニンＡ / スウィンホライドＡ / タンパク質間相互作用 / アクチン / チューブリン / 細胞毒性 / 抗腫瘍性 / 天然物化学 / 三元複合体 / アプリロニンA |
|---|
| Outline of Final Research Achievements |
Designed and synthesized aplyronine A-swinholide A hybrid, which consists of the macrolactone of aplyronine A and the side chain of swinholide A. This Hybrid retained strong cytotoxicity and actin-depolymerizing activity. In addition, hybrid induces PPI between actin and tubulin in the manner of aplyronine A. Furthermore, I conducted the structure-activity relationships about amino acid moiety by using hybrid. The trimethylserine ester group was important for potent cytotoxicity. Also, comparing the side chain analogs of aplyronine A and swinholide A, we clarified the side chain analog of aplyronine A was stronger actin-depolymerizing activity.
|
| Academic Significance and Societal Importance of the Research Achievements |
ガンは日本人の死因第一位であり、その治療法が求められる。アプリロニンＡは新規作用機序を持つ抗腫瘍活性物質であるが、天然からの供給、誘導化に制限があるため研究展開が困難である。そこで本研究では、他の天然物とのハイブリッドアナログを設計・合成し、アプリロニンＡと同様の作用機序を有する構造簡略型ハイブリッドアナログの創出に成功した。本化合物は供給・誘導の制限を緩和し、今後の研究展開が期待できる。
|
Report
(3 results)
Research Products
(17 results)
