Specific targeting of insect and vertebrate telomeres with pyrrole and imidazole polyamides

Citation
K. Maeshima et al., Specific targeting of insect and vertebrate telomeres with pyrrole and imidazole polyamides, EMBO J, 20(12), 2001, pp. 3218-3228
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
0261-4189 → ACNP
Volume
20
Issue
12
Year of publication
2001
Pages
3218 - 3228
Database
ISI
SICI code
0261-4189(20010615)20:12<3218:STOIAV>2.0.ZU;2-2
Abstract
DNA minor groove-binding compounds (polyamides) that target insect and vert ebrate telomeric repeats with high specificity were synthesized. Base pair recognition of these polyamides is based on the presence of the heterocycli c amino acids pyrrole and imidazole, One compound (TH52B) interacts uniquel y and with excellent specificity (K-d = 0.12 nM) with two consecutive insec t-type telomeric repeats (TTAGG). A related compound, TH59, displays high s pecificity (K-d = 0.5 nM) for tandem vertebrate (TTAGGG) and insect telomer ic repeats, The high affinity and specificity of these compounds were achie ved by bidentate binding of two flexibly linked DNA-binding moieties. Epifl uorescence microscopy studies show that fluorescent derivatives of TH52B an d TH59 stain insect or vertebrate telomeres of chromosomes and nuclei sharp ly. Importantly, the telomere-specific polyamide signals of HeLa chromosome s co-localize with the immunofluorescence signals of the telomere-binding p rotein TRF1. Our results demonstrate that telomere-specific compounds allow rapid estimation of relative telomere length. The insect-specific compound TH52 was shown to be incorporated rapidly into growing Sf9 cells, underlin ing the potential of these compounds for telomere biology and possibly huma n medicine.