- DEUTERATED COMPOUNDS, COMPOSITIONS, AND USES
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Deuterated polyunsaturated fatty acid ("PUFA") compounds, compositions, and uses of the compounds for reducing lipid autooxidation and the treatment of various diseases and conditions are provided.
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Paragraph 0158; 0159-0160; 0162
(2020/06/05)
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- Threshold protective effect of deuterated polyunsaturated fatty acids on peroxidation of lipid bilayers
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Autoxidation of polyunsaturated fatty acids (PUFAs) damages lipid membranes and generates numerous toxic by-products implicated in neurodegeneration, aging, and other pathologies. Abstraction of bis-allylic hydrogen atoms is the rate-limiting step of PUFA autoxidation, which is inhibited by replacing bis-allylic hydrogens with deuterium atoms (D-PUFAs). In cells, the presence of a relatively small fraction of D-PUFAs among natural PUFAs is sufficient to effectively inhibit lipid peroxidation (LPO). Here, we investigate the effect of various D-PUFAs on the stability of liposomes under oxidative stress conditions. The permeability of vesicle membranes to fluorescent dyes was measured as a proxy for bilayer integrity, and the formation of conjugated dienes was monitored as a proxy for LPO. Remarkably, both approaches reveal a similar threshold for the protective effect of D-PUFAs in liposomes. We show that protection rendered by D-PUFAs depends on the structure of the deuterated fatty acid. Our findings suggest that protection of PUFAs against autoxidation depends on the total level of deuterated bi-sallylic (CD2) groups present in the lipid bilayer. However, the phospholipid containing 6,6,9,9,12,12,15,15,18,18-d10-docosahexaenoic acid exerts a stronger protective effect than should be expected from its deuteration level. These findings further support the application of D-PUFAs as preventive/therapeutic agents in numerous pathologies that involve LPO.
- Firsov, Alexander M.,Fomich, Maksim A.,Bekish, Andrei V.,Sharko, Olga L.,Kotova, Elena A.,Saal, Harry J.,Vidovic, Dragoslav,Shmanai, Vadim V.,Pratt, Derek A.,Antonenko, Yuri N.,Shchepinov, Mikhail S.
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p. 2099 - 2117
(2019/03/27)
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- Derivatives of glycerophosphocholine and glycerophosphoethanolamine, their preparation and their use
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The invention relates to new triphenylmethyl derivatives of sn-glycero-3-phosphocholine and sn-glycero-3-phosphoethanolamine of the general formula STR1 in which T denotes a triphenylmethyl group which is unsubstituted or monosubstituted or polysubstitute
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