Queuine dihydrochloride 

Queuine dihydrochloride is a selective substrate for tRNA guanine transglycosylase (TGT) and can be incorporated into eukaryotic tRNA. Queuine dihydrochloride promotes tRNA modification, affecting mitochondrial function and Warburg metabolic phenotype. If Queuine dihydrochloride is deficient, aerobic glycolysis can be enhanced, oxidative phosphorylation can be inhibited, and Warburg metabolism can be promoted, accompanied by increased ammonia and lactate production and increased lactate dehydrogenase activity. Queuine dihydrochloride can be used for autoimmune diseases (such as experimental models of multiple sclerosis) and cancer metabolic regulation, and its deficiency is associated with low tRNA modification in tumor cells^[1][2][3].

Queuine dihydrochloride (1 μM; 5 days, supplemented every 24 h) reduces lactate dehydrogenase (LDH) activity in HeLa cells compared to the Queuine dihydrochloride group and limits glucose consumption and lactate production. In the absence of Queuine dihydrochloride, cells exhibits Warburg-type metabolic characteristics^[2].
Queuine dihydrochloride is a natural substrate of TGT and irreversibly replaces guanine (G34) in tRNA by human TGTase^[2].
Queuine dihydrochloride is a modified pyrrolopyrimidine nucleoside synthesized only by bacteria. It irreversibly replaces guanine (G34) in the tRNA anticodon loop by eukaryotic tRNA guanine transglycosylase (TGT) to form queuosine nucleotides, which specifically modify tRNA isoacceptors corresponding to aspartic acid, asparagine, histidine and tyrosine^[3].
Queuine dihydrochloride's biological activity is reflected in the following aspects: Queuine dihydrochloride deficiency is a characteristic of rapidly proliferating cells (such as tumor cells and activated T cells in autoimmune diseases), and it can regulate cell metabolism by affecting the accuracy of tRNA translation, such as promoting Warburg-type metabolism (enhancing aerobic glycolysis and inhibiting oxidative phosphorylation)^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In the tRNA modification defect model of Qtrt1^Gt/Gt mice, which lack endogenous queuine due to gene knockout, liver mitochondrial dysfunction, decreases ATP levels, and alteres electron transport chain activity were observed^[3].
Queuine (30 mg/kg, 100 μL; intraperitoneal injection; once a day; 5 days) dihydrochloride has no significant effect on the EAE score of the mouse experimental autoimmune encephalomyelitis (EAE) model, but reduces the tRNA low modification level of splenocyte CD4⁺ T cells^[3].
TGT substrate design based on Queuine (such as 6-thioguanine 6TG, novel synthetic substrate NPPDAG) shows significant therapeutic effects in the mouse EAE model. NPPDAG selectively inhibits effector T cell proliferation and central nervous system infiltration through TGT-mediated tRNA modification, reduces the release of proinflammatory cytokines (such as IL-17 and IFN-γ), and completely reverses the clinical symptoms of EAE mice. It is ineffective in TGT-deficient mice, confirming the TGT-dependent therapeutic mechanism^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

350.20

C₁₂H₁₇Cl₂N₅O₃

86496-18-6

Solid

White to off-white

O[C@@H]([C@H](C=C1)O)[C@H]1NCC2=CNC(NC(N)=N3)=C2C3=O.[H]Cl.[H]Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Yifeng Yuan, et al. Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens. Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):19126-19135.  [Content Brief]