| Project/Area Number |
25893258
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | Tokyo University of Pharmacy and Life Science |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2013-08-30 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | リードスルー / ネガマイシン / デュシェンヌ型筋ジストロフィー / 創薬化学 / 抗生物質 |
|---|
| Outline of Final Research Achievements |
(+)-Negamycin, a natural dipeptidic antibiotic, exhibits a readthrough activity toward the nonsense mutation. We performed a structure activity relationship study for development of nonsense mutation disease therapeutics. As a result, we successful obtained that TCP-112 shows a higher readthrough activity than negamycin. In this study, further derivatization at the carboxylic acid part of TCP-112 demonstrates that m-chlorobenzyl ester derivative exhibits a more potent readthrough activity than TCP-112 in cell-based assay. However, in the cell-free protein expression system, the readthrough activity of m-chlorobenzyl ester derivative drastically decreases compared to that in the cell-based assay. These results suggest that benzyl ester-type derivatives enhance the hydrophobicity and function as prodrugs to produce TCP-112 in living cell systems.
|
