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The Potential of Telomeric G-quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils

1
Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia
2
Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia
3
Lomonosov Moscow State University, Department of Chemistry, Moscow 119234, Russia
4
Lomonosov Moscow State University, Department of Chemistry, Moscow 119234, Russia
5
National Research Center for Hematology, Russia Federation Ministry of Public Health, Moscow 125167, Russia
6
Gamaleya National Research Centre of Epidemiology and Microbiology, Moscow 123098, Russia
7
Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(2), 249; https://doi.org/10.3390/biom10020249
Received: 20 December 2019 / Revised: 28 January 2020 / Accepted: 4 February 2020 / Published: 6 February 2020
Human neutrophils are the first line of defense against bacterial and viral infections. They eliminate pathogens through phagocytosis, which activate the 5-lipoxygenase (5-LOX) pathway resulting in synthesis of leukotrienes. Using HPLC analysis, flow cytometry, and other biochemical methods, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs) able to fold into G-quadruplex structures on the main functions of neutrophils. Designed ODNs contained four human telomere TTAGGG repeats (G4) including those with phosphorothioate oligoguanosines attached to the end(s) of G-quadruplex core. Just modified analogues of G4 was shown to more actively than parent ODN penetrate into cells, improve phagocytosis of Salmonella typhimurium bacteria, affect 5-LOX activation, the cytosol calcium ion level, and the oxidative status of neutrophils. As evident from CD and UV spectroscopy data, the presence of oligoguanosines flanking G4 sequence leads to dramatic changes in G-quadruplex topology. While G4 folds into a single antiparallel structure, two main folded forms have been identified in solutions of modified ODNs: antiparallel and dominant, more stable parallel. Thus, both the secondary structure of ODNs and their ability to penetrate into the cytoplasm of cells are important for the activation of neutrophil cellular effects. Our results offer new clues for understanding the role of G-quadruplex ligands in regulation of integral cellular processes and for creating the antimicrobial agents of a new generation.
Keywords: neutrophils; phagocytosis; leukotrienes; oligodeoxyribonucleotides; G-quadruplexes; salmonella neutrophils; phagocytosis; leukotrienes; oligodeoxyribonucleotides; G-quadruplexes; salmonella
MDPI and ACS Style

Golenkina, E.A.; Viryasova, G.M.; Dolinnaya, N.G.; Bannikova, V.A.; Gaponova, T.V.; Romanova, Y.M.; F.Sud’ina, G. The Potential of Telomeric G-quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils. Biomolecules 2020, 10, 249.

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