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Updated: Feb 5, 2026
A G-quadruplex DNA-affinity Approach for Purification of Enzymatically Active G4 Resolvase1
Published on: March 18, 2017
G-quadruplex-forming oligodeoxyribonucleotides activate leukotriene synthesis in human neutrophils
Galina M Viryasova1, Nina G Dolinnaya2, Ekaterina A Golenkina1
1a Belozersky Institute of Physico-Chemical Biology , Lomonosov Moscow State University , Moscow , Russia.
Abstract:
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)) 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. Communicated by Ramaswamy H. Sarma.
Insights
G-quadruplex DNA structures enhance the immune response by boosting leukotriene synthesis in human neutrophils during bacterial infections. This G-quadruplex formation is crucial for activating the 5-lipoxygenase pathway in host defense.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Human polymorphonuclear leukocytes (PMNLs) are critical for fighting bacterial and fungal infections via phagocytosis.
- The 5-lipoxygenase (5-LOX) pathway is activated during phagocytosis, producing leukotrienes that mediate host defense.
Purpose of the Study:
- To investigate the role of G-quadruplex-forming oligodeoxyribonucleotides (ODNs) in regulating 5-LOX pathway activation in human neutrophils.
- To explore the structural and functional aspects of G-quadruplex ODNs and their analogues.
Main Methods:
- Designed and synthesized a library of ODNs with human telomeric repeats and modified linkages/substitutions.
- Studied the structural and functional properties of these ODNs, focusing on G-quadruplex formation.
- Assessed the effect of exogenous G-quadruplex ODNs on 5-LOX metabolite formation in neutrophils exposed to Salmonella Typhimurium.
Main Results:
- Exogenous G-quadruplex-forming ODNs significantly enhanced 5-LOX metabolite formation in human neutrophils challenged with Salmonella Typhimurium.
- G-quadruplex formation was essential for this enhancement; substitutions preventing G-quadruplex folding abolished leukotriene synthesis activation.
- This study demonstrates G-quadruplex structures as potent regulators of 5-LOX product synthesis.
Conclusions:
- G-quadruplex structures are key regulators of the 5-lipoxygenase pathway in human neutrophils during phagocytosis of microbial pathogens.
- The findings highlight a novel mechanism by which G-quadruplexes modulate innate immune responses.
- This research opens avenues for therapeutic strategies targeting G-quadruplex structures in infectious diseases.
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