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Open AccessArticle

Bimodular Antiparallel G-Quadruplex Nanoconstruct with Antiproliferative Activity

1
Chemistry Department, Lomonosov Moscow State University, Leninskiye Gory 1–40, 119991 Moscow, Russia
2
Institute of Gene Biology, Russian Academy of Sciences, Vavilova 34/5, 119334 Moscow, Russia
3
Federal State Autonomous Institution (N.N. Burdenko National Scientific and Practical Center for Neurosurgery) of the Ministry of Health of the Russian Federation, 1st Tverskaya-Yamskaya 13/5, 125047 Moscow, Russia;
4
Sechenov First Moscow State Medical University, Institute of Molecular Medicine, B. Pyrogovskaya 2/6, Moscow 119992, Russia
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(19), 3625; https://doi.org/10.3390/molecules24193625
Received: 29 July 2019 / Revised: 23 September 2019 / Accepted: 28 September 2019 / Published: 8 October 2019
(This article belongs to the Special Issue Aptamers: Successes, Limitations and Future Directions)
Oligonucleotides with an antiproliferative activity for human cancer cells have attracted attention over the past decades; many of them have a G-quadruplex structure (GQ), and a cryptic target. In particular, DNA oligonucleotide HD1, a minimal GQ, could inhibit proliferation of some cancer cell lines. The HD1 is a 15-nucleotide DNA oligonucleotide that folds into a minimal chair-like monomolecular antiparallel GQ structure. In this study, for eight human cancer cell lines, we have analyzed the antiproliferative activities of minimal bimodular DNA oligonucleotide, biHD1, which has two HD1 modules covalently linked via single T-nucleotide residue. Oligonucleotide biHD1 exhibits a dose-dependent antiproliferative activity for lung cancer cell line RL-67 and cell line of central nervous system cancer U87 by MTT-test and Ki-67 immunoassay. The study of derivatives of biHD1 for the RL-67 and U87 cell lines revealed a structure-activity correlation of GQ folding and antiproliferative activity. Therefore, a covalent joining of two putative GQ modules within biHD1 molecule provides the antiproliferative activity of initial HD1, opening a possibility to design further GQ multimodular nanoconstructs with antiproliferative activity—either as themselves or as carriers. View Full-Text
Keywords: DNA G-quadruplex oligonucleotide; nanoconstruct; antiproliferative activity; human cancer cell lines DNA G-quadruplex oligonucleotide; nanoconstruct; antiproliferative activity; human cancer cell lines
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Antipova, O.; Samoylenkova, N.; Savchenko, E.; Zavyalova, E.; Revishchin, A.; Pavlova, G.; Kopylov, A. Bimodular Antiparallel G-Quadruplex Nanoconstruct with Antiproliferative Activity. Molecules 2019, 24, 3625.

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