Chimeric bifunctional oligonucleotides as a novel tool to invade telomerase assembly

被引：8

作者：

Azhibek, Dulat ^{[1
,2
,3
]}

Zvereva, Maria ^{[1
,2
]}

Zatsepin, Timofei ^{[1
,2
,3
]}

Rubtsova, Maria ^{[1
,2
]}

Dontsova, Olga ^{[1
,2
]}

机构：

[1] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia

[2] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119992, Russia

[3] Skolkovo Inst Sci & Technol, Odintsovsky Dist 143025, Moscow Region, Russia

来源：

NUCLEIC ACIDS RESEARCH | 2014年 / 42卷 / 15期

基金：

俄罗斯科学基金会;

关键词：

REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT; DNA-SYNTHESIS; RNA; INHIBITION; CANCER; CELLS; SEQUENCE; REQUIRES; PROBES;

D O I：

10.1093/nar/gku688

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：9531 / 9542

页数：12

共 35 条

[1] Reconstitution of human telomerase activity and identification of a minimal functional region of the human telomerase RNA [J].