The Potential of Telomeric G-quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophilsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 апреля 2020 г.
Аннотация: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.