Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Institute for Integrated Cell-Material Science (WPI-iCeMS), Kyoto University, Sakyo, Kyoto 6060-8501, Japan.
J Am Chem Soc. 2020 Oct 14;142(41):17356-17363. doi: 10.1021/jacs.0c04955. Epub 2020 Oct 6.
Telomeres are closely associated with cellular senescence and cancer. Although some techniques have been developed to label telomeres in living cells for study of telomere dynamics, few biocompatible near-infrared probes based on synthetic molecules have been reported. In this study, we developed a near-infrared fluorogenic pyrrole-imidazole polyamide probe () to visualize telomeres by conjugating a silicon-rhodamine () fluorophore with a tandem tetramer pyrrole-imidazole polyamide targeting 24 bp in the telomeric double-stranded (ds) DNA. was almost nonfluorescent in water but increased its fluorescence dramatically on binding to telomeric dsDNA. Using a peptide-based delivery reagent, we demonstrated the specific and effective visualization of telomeres in living U2OS cells. Moreover, could be used to observe the dynamic movements of telomeres during interphase and mitosis. This simple imaging method using a synthetic near-infrared probe could be a powerful tool for studies of telomeres and for diagnosis.
端粒与细胞衰老和癌症密切相关。虽然已经开发出一些技术来标记活细胞中的端粒，以研究端粒动力学，但很少有基于合成分子的生物相容性近红外探针被报道。在这项研究中，我们开发了一种近红外荧光吡咯并咪唑聚酰胺探针（），通过将硅罗丹明（）荧光团与串联四聚体吡咯并咪唑聚酰胺偶联，该聚酰胺靶向端粒双链 DNA 中的 24 个碱基对，从而可视化端粒。在水中几乎没有荧光，但与端粒双链 DNA 结合后，其荧光显著增强。使用基于肽的递药试剂，我们在活 U2OS 细胞中证明了端粒的特异性和有效可视化。此外，可用于观察有丝分裂间期和有丝分裂中端粒的动态运动。这种使用合成近红外探针的简单成像方法可能是研究端粒和诊断的有力工具。
