G-quadruplex-forming oligodeoxyribonucleotides activate leukotriene synthesis in human neutrophilsстатья

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Дата последнего поиска статьи во внешних источниках: 3 сентября 2019 г.

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[1] G-quadruplex-forming oligodeoxyribonucleotides activate leukotriene synthesis in human neutrophils / G. M. Viryasova, N. G. Dolinnaya, E. A. Golenkina et al. // Journal of Biomolecular Structure and Dynamics. — 2019. — Vol. 37, no. 14. — P. 3649–3659. Human polymorphonuclear leukocytes (PMNLs, neutrophils) play a major role in the immune response to bacterial and fungal infections and eliminate pathogens through phagocytosis. During phagocytosis of microorganisms, the 5-lipoxygenase (5-LOX) pathway is activated resulting in generation of leukotrienes, which mediate host defense. In this study, a library of oligodeoxyribonucleotides (ODNs) with varying numbers of human telomeric repeats (d(TTAGGG)n) and their analogues with phosphorothioate internucleotide linkages and single-nucleotide substitutions was designed. These ODNs with the potential to fold into G-quadruplex structures were studied from structural and functional perspectives. We showed that exogenous G-quadruplex-forming ODNs significantly enhanced 5-LOX metabolite formation in human neutrophils exposed to Salmonella Typhimurium bacteria. However, the activation of leukotriene synthesis was completely lost when G-quadruplex formation was prevented by substitution of guanosine with 7-deazaguanosine or adenosine residues at several positions. To our knowledge, this study is the first to demonstrate that G-quadruplex structures are potent regulators of 5-LOX product synthesis in human neutrophils in the presence of targets of phagocytosis. [ DOI ]

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