G4 Sensing Pyridyl-Thiazole Polyamide Represses c-KIT Expression in Leukemia Cells
| Autor: | Jyotirmayee Dash, Manish Debnath, Debasish Dutta, Tania Das, Raj Paul |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell
010402 general chemistry G-quadruplex Ligands 01 natural sciences Proto-Oncogene Mas Catalysis chemistry.chemical_compound Gene expression medicine Humans Thiazole Promoter Regions Genetic Leukemia Oncogene 010405 organic chemistry Organic Chemistry General Chemistry 0104 chemical sciences Cell biology G-Quadruplexes Nylons Thiazoles medicine.anatomical_structure chemistry Cancer cell Nucleic acid DNA |
| Zdroj: | Chemistry (Weinheim an der Bergstrasse, Germany). 27(33) |
| ISSN: | 1521-3765 |
| Popis: | Specific sensing and functional tuning of nucleic acid secondary structures remain less explored to date. Herein, we report a thiazole polyamide TPW that binds specifically to c-KIT1 G-quadruplex (G4) with sub-micromolar affinity and ∼1 : 1 stoichiometry and represses c-KIT proto-oncogene expression. TPW shows up to 10-fold increase in fluorescence upon binding with c-KIT1 G4, but shows weak or no quantifiable binding to other G4s and ds26 DNA. TPW can increase the number of G4-specific antibody (BG4) foci and mark G4 structures in cancer cells. Cell-based assays reveal that TPW can efficiently repress c-KIT expression in leukemia cells via a G4-dependent process. Thus, the polyamide can serve as a promising probe for G-quadruplex recognition with the ability to specifically alter c-KIT oncogene expression. |
| Databáze: | OpenAIRE |
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