Open AccessA Near-Infrared Fluorogenic Pyrrole–Imidazole Polyamide Probe for Live-Cell Imaging of Telomeres
Author(s) -
Yutaro Tsubono,
Yusuke Kawamoto,
Takehiko Hidaka,
Ganesh N. Pandian,
Kaori Hashiya,
Toshikazu Bando,
Hiroshi Sugiyama
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c04955
Subject(s) - chemistry , telomere , fluorophore , rhodamine , live cell imaging , fluorescence , dna , guanine , biophysics , imidazole , cell , biochemistry , nucleotide , physics , biology , quantum mechanics , gene
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 ( SiR-TTet59B ) to visualize telomeres by conjugating a silicon-rhodamine ( SiR ) fluorophore with a tandem tetramer pyrrole-imidazole polyamide targeting 24 bp in the telomeric double-stranded (ds) DNA. SiR-TTet59B 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, SiR-TTet59B 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.