Department of Molecular Chemistry (DCM), CNRS, UMR 5250, Université Grenoble-Alpes, 38000 Grenoble, France.
CNRS UMR9187, INSERM U1196, Institut Curie, PSL Research University, F-91405 Orsay, France.
Molecules. 2023 Jan 10;28(2):682. doi: 10.3390/molecules28020682.
During the last decade, the evidence for the biological relevance of i-motif DNA (i-DNA) has been accumulated. However, relatively few molecules were reported to interact with i-DNA, and a controversy concerning their binding mode, affinity, and selectivity persists in the literature. In this context, the cholestane derivative has been reported to modulate gene expression by stabilizing an i-motif structure in its promoter. In the present contribution, we report on a novel, more straightforward, synthesis of requiring fewer steps compared to the previous approach. Furthermore, the interaction of with four different i-motif DNA sequences was thoroughly investigated by bio-layer interferometry (BLI) and circular dichroism (CD) spectroscopy. Surprisingly, our results show that is a very weak ligand of i-DNA as no quantifiable interaction or significant stabilization of i-motif structures could be observed, stimulating a quest for an alternative mechanism of its biological activity.
在过去的十年中，i-motif DNA（i-DNA）的生物学相关性证据不断积累。然而，据报道，与 i-DNA 相互作用的分子相对较少，并且关于它们的结合模式、亲和力和选择性的争议在文献中仍然存在。在这种情况下，胆甾烷衍生物 被报道通过稳定其启动子中的 i-motif 结构来调节 基因表达。在本研究中，我们报道了一种新的、更直接的 合成方法，与之前的方法相比，所需步骤更少。此外，通过生物层干涉（BLI）和圆二色性（CD）光谱法，我们还彻底研究了 与四个不同的 i-motif DNA 序列的相互作用。令人惊讶的是，我们的结果表明， 是 i-DNA 的非常弱的配体，因为没有观察到可量化的相互作用或 i-motif 结构的显著稳定，这促使人们寻求其生物活性的替代机制。
