School of Chemical Sciences, Indian Association for the Cultivation of Science, Kolkata, 700032, India.
Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe, University Frankfurt, Max-von-Laue Strasse 7, 60438, Frankfurt am Main, Germany.
Nat Commun. 2024 Jun 20;15(1):5275. doi: 10.1038/s41467-024-49534-0.
DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA binding peptide mimic TBP2, which forms transmembrane ion channels, impacting cellular ion concentration and consequently stabilizing G-quadruplex DNA structures. TBP2 self-assembles into nanostructures, e.g., vesicles and nanofibers and facilitates the transportation of Na and K across lipid membranes with high conductance (~0.6 nS). Moreover, TBP2 exhibits increased fluorescence when incorporated into the membrane or in cellular nuclei. Monomeric TBP2 can enter the lipid membrane and localize to the nuclei of cancer cells. The coordinated process of time-dependent membrane or nuclear localization of TBP2, combined with elevated intracellular cation levels and direct G-quadruplex (G4) interaction, synergistically promotes formation and stability of G4 structures, triggering cancer cell death. This study introduces a platform to mimic and control intricate biological functions, leading to the discovery of innovative therapeutic approaches.
DNA 结合转录因子具有与脂质膜相互作用的能力，从而构建离子可渗透的途径。在此，我们提出了一种基于噻唑的 DNA 结合肽模拟物 TBP2，它可以形成跨膜离子通道，影响细胞内离子浓度，从而稳定 G-四链体 DNA 结构。TBP2 自组装成纳米结构，例如囊泡和纳米纤维，并促进 Na 和 K 穿过脂质膜的高电导(~0.6 nS)运输。此外，TBP2 掺入膜或细胞核时会发出增强的荧光。单体 TBP2 可以进入脂质膜并定位于癌细胞的核内。TBP2 的膜或核定位的时间依赖性协调过程，加上细胞内阳离子水平的升高和直接的 G-四链体(G4)相互作用，协同促进 G4 结构的形成和稳定性，引发癌细胞死亡。这项研究引入了一个模拟和控制复杂生物功能的平台，从而发现了创新的治疗方法。
