title: Chimeric bifunctional oligonucleotides as a novel tool to invade telomerase assembly.
abstract: Telomerase is a key participant in the telomere length maintaining system in eukaryotic cells. Telomerase RNA and protein reverse transcriptase subunits are essential for the appearance of active telomerase in vitro. Telomerase is active in many cancer types and is a potential target for anticancer drug development. Here we report a new approach for impairing telomerase function at the stage of human telomerase assembly. The approach is based on the application of chimeric bifunctional oligonucleotides that contain two oligonucleotide parts complementary to the functional domains of telomerase RNA connected with non-nucleotide linkers in different orientations (5'-3', 5'-5' or 3'-3'). Such chimeras inhibited telomerase in vitro in the nM range, but were effective in vivo in sub-nM concentrations, predominantly due to their effect on telomerase assembly and dimerization.
authors: Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992, Russian Federation Skolkovo Institute of Science and Technology, Novaya Street, 100, Skolkovo, Odintsovsky District, Moscow Region, 143025, Russian Federation.
authors: Dulat
authors: D
authors: Azhibek
authors: Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992, Russian Federation zvereva@genebee.msu.ru.
authors: Maria
authors: M
authors: Zvereva
authors: Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992, Russian Federation Skolkovo Institute of Science and Technology, Novaya Street, 100, Skolkovo, Odintsovsky District, Moscow Region, 143025, Russian Federation.
authors: Timofei
authors: T
authors: Zatsepin
authors: Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992, Russian Federation.
authors: Maria
authors: M
authors: Rubtsova
authors: Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992, Russian Federation.
authors: Olga
authors: O
authors: Dontsova
mesh_terms: D019281:Dimerization; D057809:HEK293 Cells; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D009841:Oligonucleotides; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase