2021 Fiscal Year Final Research Report
Small molecules that induce atypical ubiquitinations
Project/Area Number |
19K16326
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
|
Research Institution | Tohoku University |
Principal Investigator |
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Keywords | 疎水性タグ / mHtt |
Outline of Final Research Achievements |
Ubiquitination, a posttranslational modification, has been shown to have variety in its linkage type. Here I aimed to generate compounds able to induce atypical ubiquitinations. Compounds that can display hydrophobic structure on protein surface were synthesized and are found to mediate targeted degradation of mHtt via ubiquitin-proteasome system. The results were reported in an international conference and were published in an international academic journal.
|
Free Research Field |
創薬化学
|
Academic Significance and Societal Importance of the Research Achievements |
本研究で得られた化合物は通常のユビキチン化経路とは異なる経路でユビキチン化を誘導しタンパク質を分解するため、特殊なユビキチン化を誘導している可能性が考えられる。本化合物についてさらなる解析が必要だが、特殊なユビキチン化に関する研究を支援するケミカルツールになりうる。 また、化合物によって減少したmHttは神経変性疾患の原因となるタンパク質であり。この化合物は脳移行性も示したことから、神経変性疾患の新規治療戦略の提案につながった。
|