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Updated: Apr 26, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Chimeric bifunctional oligonucleotides as a novel tool to invade telomerase assembly
Dulat Azhibek1, Maria Zvereva2, Timofei Zatsepin1
1Department 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.
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.
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