| Autor: |
Angelbello AJ; Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, United States., Disney MD; Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
ACS chemical biology [ACS Chem Biol] 2020 Jul 17; Vol. 15 (7), pp. 1820-1825. Date of Electronic Publication: 2020 Jun 17. |
| DOI: |
10.1021/acschembio.0c00417 |
| Abstrakt: |
Expanded RNA repeats cause more than 30 incurable diseases. One approach to mitigate their toxicity is by using small molecules that assemble into potent, oligomeric species upon binding to the disease-causing RNA in cells. Herein, we show that the expanded repeat [r(CUG) exp ] that causes myotonic dystrophy type 1 (DM1) catalyzes the in situ synthesis of its own inhibitor using an RNA-templated tetrazine ligation in DM1 patient-derived cells. The compound synthesized on-site improved DM1-associated defects at picomolar concentrations, enhancing potency by 10 000-fold, compared to its parent compounds that cannot undergo oligomerization. A fluorogenic reaction is also described where r(CUG) exp templates the synthesis of its own imaging probe to enable visualization of the repeat in its native context in live cells and muscle tissue. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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