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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.

Authors
  • Golenkina, Ekaterina A1
  • Viryasova, Galina M1
  • Dolinnaya, Nina G2
  • Bannikova, Valeria A2
  • Gaponova, Tatjana V3
  • Romanova, Yulia M4
  • Sud'ina, Galina F1
  • 1 Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia.
  • 2 Lomonosov Moscow State University, Department of Chemistry, Moscow 119234, Russia.
  • 3 National Research Center for Hematology, Russia Federation Ministry of Public Health, Moscow 125167, Russia.
  • 4 Gamaleya National Research Centre of Epidemiology and Microbiology, Moscow 123098, Russia.
Type
Published Article
Journal
Biomolecules
Publisher
MDPI AG
Publication Date
Feb 06, 2020
Volume
10
Issue
2
Identifiers
DOI: 10.3390/biom10020249
PMID: 32041263
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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