Rota Sperti Francesco, Mitteaux Jérémie, Zell Joanna, Pipier Angélique, Valverde Ibai E, Monchaud David
ICMUB, CNRS UMR6302, Université de Bourgogne 9 Avenue Alain Savary 21078 Dijon France
RSC Chem Biol. 2023 May 16;4(7):456-465. doi: 10.1039/d3cb00009e. eCollection 2023 Jul 5.
Chemical biology hinges on multivalent molecular tools that can specifically interrogate and/or manipulate cellular circuitries from the inside. The success of many of these approaches relies on molecular tools that make it possible to visualize biological targets in cells and then isolate them for identification purposes. To this end, click chemistry has become in just a few years a vital tool in offering practically convenient solutions to address highly complicated biological questions. We report here on two clickable molecular tools, the biomimetic G-quadruplex (G4) ligands MultiTASQ and MultiTASQ, which benefit from the versatility of two types of bioorthogonal chemistry, CuAAC and SPAAC (the discovery of which was very recently awarded the Nobel Prize of chemistry). These two MultiTASQs are used here to both visualize G4s in and identify G4s from human cells. To this end, we developed click chemo-precipitation of G-quadruplexes (G4-click-CP) and G4 click imaging protocols, which provide unique insights into G4 biology in a straightforward and reliable manner.
化学生物学依赖于多价分子工具，这些工具能够从内部特异性地探究和/或操纵细胞回路。许多这些方法的成功依赖于分子工具，这些工具使在细胞中可视化生物靶点并随后将其分离以进行鉴定成为可能。为此，点击化学在短短几年内已成为一种至关重要的工具，可提供切实方便的解决方案来解决高度复杂的生物学问题。我们在此报告两种可点击的分子工具，即仿生G-四链体（G4）配体MultiTASQ和MultiTASQ，它们受益于两种生物正交化学的多功能性，即铜催化的叠氮化物-炔烃环加成反应（CuAAC）和应变促进的炔烃-叠氮化物环加成反应（SPAAC）（其发现最近获得了诺贝尔化学奖）。这里使用这两种MultiTASQ在人细胞中可视化G4并从人细胞中鉴定G4。为此，我们开发了G-四链体的点击化学沉淀法（G4-click-CP）和G4点击成像方案，它们以直接且可靠的方式为G4生物学提供了独特的见解。
