Development of small molecule ligands to inhibit expansion of CAG trinulceotide repeat
| Project/Area Number |
15K17885
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Bio-related chemistry
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
Yamada Takeshi 大阪大学, 産業科学研究所, 特任助教(常勤) (80633263)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | トリヌクレオチドリピート / トリンクレオチドリピート / 核酸 / 低分子 / ケミカルバイオロジー / トリプレットリピート / 有機合成 |
|---|
| Outline of Final Research Achievements |
Trinucleotide repeat disease is a group of neurodegenerative disorders, due to excessive elongation of 5'-CNG-3' (N = A, C, G and T) repeat sequences in genome. We previously developed a small molecule NA and NCD, which strongly bound to AA and GG mismatches in CAG and CGG repeats with 2 : 1 stoichiometry and high cooperativity, respectively. Based on those results, a series of DNA binding molecules NA-Cn-SH and NCD-Cn-SH in which the mismatch binding domain and a thiol moiety are linked via a linker were developed. Those thiol derivatives oxidatively dimerized under aerobic conditions. The reaction rate of the dimerization was dramatically accelerated in the presence of corresponding repeat DNA. These results suggested that NA-Cn-SH and NCD-Cn-SH selectively accumulated on targeting repeat DNA, resulting in the formation of a dimer with higher thermal stability, and are attractive for the chemical biological studies focusing on trinucleotide repeat diseases.
|
Report
(4 results)
Research Products
(7 results)
