School of Chemical Sciences, Indian Association for the Cultivation of Science, Kolkata, 700032, India.
Chemistry. 2021 Jun 10;27(33):8590-8599. doi: 10.1002/chem.202100907. Epub 2021 May 5.
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.
迄今为止，对核酸二级结构的特异性传感和功能调整的研究还较少。本文报道了一种噻唑聚酰胺 TPW，它能以亚毫摩尔亲和力和 1:1 的化学计量比特异性结合 c-KIT1 G-四链体（G4），并抑制 c-KIT 原癌基因的表达。TPW 与 c-KIT1 G4 结合后荧光强度增加了 10 倍，但与其他 G4 和 ds26 DNA 的结合较弱或无法定量检测。TPW 可以增加 G4 特异性抗体（BG4）焦点的数量，并标记癌细胞中的 G4 结构。基于细胞的测定表明，TPW 可以通过 G4 依赖的过程有效地抑制白血病细胞中的 c-KIT 表达。因此，这种聚酰胺可用作一种有前途的 G-四链体识别探针，具有特异性改变 c-KIT 癌基因表达的能力。
