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Article

Covalent Bi-Modular Parallel and Antiparallel G-Quadruplex DNA Nanocostructs Reduce Viability of Patient Glioma Primary Cell Cultures

by
Valeria Legatova
1,
Nadezhda Samoylenkova
2,
Alexander Arutyunyan
3,
Vadim Tashlitsky
3,
Elena Zavyalova
1,
Dmitry Usachev
2,
Galina Pavlova
2,4,5,* and
Alexey Kopylov
1,*
1
Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, Russia
2
Burdenko Neurosurgical Institute, 125047 Moscow, Russia
3
Belozersky Research Institute of Physical Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia
4
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia
5
Department of Medical Genetics, Sechenov First Moscow State Medical University, 119991 Moscow, Russia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(7), 3372; https://doi.org/10.3390/ijms22073372
Submission received: 27 February 2021 / Revised: 19 March 2021 / Accepted: 22 March 2021 / Published: 25 March 2021
(This article belongs to the Special Issue Oligonucleotide, Therapy, and Applications)
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Abstract

G-quadruplex oligonucleotides (GQs) exhibit specific anti-proliferative activity in human cancer cell lines, and they can selectively inhibit the viability/proliferation of cancer cell lines vs. non-cancer ones. This ability could be translated into a cancer treatment, in particular for glioblastoma multiform (GBM), which currently has a poor prognosis and low-efficiency therapeutic treatments. A novel bi-modular GQ, bi-(AID-1-T), a twin of the previously described three-quartet AID-1-T, was designed and studied in terms of both its structure and function. A covalent conjugation of two AID-1-Ts via three thymidine link, TTT, did not interfere with its initial GQ structure. A comparison of bi-(AID-1-T) with its mono-modular AID-1-T, mono-modular two-quartet HD1, and bi-modular bi-HD1, as well as conventional two-quartet AS1411, was made. Among the five GQs studied, bi-(AID-1-T) had the highest anti-proliferative activity for the neural cancer cell line U87, while not affecting the control cell line, human embryonic fibroblasts. GQs, for the first time, were tested on several primary glioma cultures from patient surgical samples. It turned out that the sensitivity of the patient primary glioma cultures toward GQs varied, with an apparent IC50 of less than 1 μM for bi-(AID-1-T) toward the most sensitive G11 cell culture (glioma, Grade III).
Keywords: G-quadruplexes; covalent dimer construct; anti-proliferative activity; primary cell culture of human glioma G-quadruplexes; covalent dimer construct; anti-proliferative activity; primary cell culture of human glioma

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MDPI and ACS Style

Legatova, V.; Samoylenkova, N.; Arutyunyan, A.; Tashlitsky, V.; Zavyalova, E.; Usachev, D.; Pavlova, G.; Kopylov, A. Covalent Bi-Modular Parallel and Antiparallel G-Quadruplex DNA Nanocostructs Reduce Viability of Patient Glioma Primary Cell Cultures. Int. J. Mol. Sci. 2021, 22, 3372. https://doi.org/10.3390/ijms22073372

AMA Style

Legatova V, Samoylenkova N, Arutyunyan A, Tashlitsky V, Zavyalova E, Usachev D, Pavlova G, Kopylov A. Covalent Bi-Modular Parallel and Antiparallel G-Quadruplex DNA Nanocostructs Reduce Viability of Patient Glioma Primary Cell Cultures. International Journal of Molecular Sciences. 2021; 22(7):3372. https://doi.org/10.3390/ijms22073372

Chicago/Turabian Style

Legatova, Valeria, Nadezhda Samoylenkova, Alexander Arutyunyan, Vadim Tashlitsky, Elena Zavyalova, Dmitry Usachev, Galina Pavlova, and Alexey Kopylov. 2021. "Covalent Bi-Modular Parallel and Antiparallel G-Quadruplex DNA Nanocostructs Reduce Viability of Patient Glioma Primary Cell Cultures" International Journal of Molecular Sciences 22, no. 7: 3372. https://doi.org/10.3390/ijms22073372

APA Style

Legatova, V., Samoylenkova, N., Arutyunyan, A., Tashlitsky, V., Zavyalova, E., Usachev, D., Pavlova, G., & Kopylov, A. (2021). Covalent Bi-Modular Parallel and Antiparallel G-Quadruplex DNA Nanocostructs Reduce Viability of Patient Glioma Primary Cell Cultures. International Journal of Molecular Sciences, 22(7), 3372. https://doi.org/10.3390/ijms22073372

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