925-14-4Relevant articles and documents
Stereochemistry, lipid length and branching influences Mincle agonist activity of monoacylglycerides
Khan, Ayesha,Braganza, Chriselle D.,Kodar, Kristel,Timmer, Mattie S. M.,Stocker, Bridget L.
, p. 425 - 430 (2020/02/03)
Herein, we report on the synthesis of a series of enantiomerically pure linear, iso-branched, and α-branched monoacyl glycerides (MAGs) in 63-72% overall yield. The ability of the MAGs to signal through human macrophage inducible C-type lectin (hMincle) using NFAT-GFP reporter cells was explored, as was the ability of the compounds to activate human monocytes. From these studies, MAGs with an acyl chain length ≥C22 were required for Mincle activation and the production of interleukin-8 (IL-8) by human monocytes. Moreover, the iso-branched MAGs led to a more pronounced immune response compared to linear MAGs, while an α-branched MAG containing a C-32 acyl chain activated cells to a higher degree than trehalose dibehenate (TDB), the prototypical Mincle agonist. Across the compound classes, the activity of the sn-1 substituted isomers was greater than the sn-3 counterparts. None of the representative compounds were cytotoxic, thus mitigating cytotoxicity as a potential mediator of cellular activity. Taken together, 6h (sn-1, iC26+1), 8a (sn-1, C32) and 8b (sn-3, C32) exhibited the best immunostimulatory properties and thus, have potential as vaccine adjuvants.
Method for synthesizing high-content fatty acid monoglyceride and co-producing nano SiO2
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Paragraph 0049; 0052; 0053, (2019/03/28)
The invention belongs to the field of fatty acid glyceride synthesis and nano powder preparation, relates to a method for synthesizing high-content fatty acid monoglyceride and co-producing nano SiO2,and particularly relates to a method for synthesizing fatty acid monoglyceride and co-producing the nano SiO2 by long-chain fatty acid and glycerinum. The method comprises the following steps of: using silicon tetrachloride to react with the glycerinum, so as to enable the glycerinum to be partially esterified to generate silicic acid glyceride; and performing an esterification reaction with fatty acid to generate fatty acid silicic acid glyceride; finally using high-activity (instability) of silicate ester, hydrolyzing in a mild condition, synthesizing the high-content fatty acid monoglyceride, and by-producing SiO2 powder in a nano state. So that a fatty acid monoglyceride product is high-selectively obtained and nano SiO2 powder is co-produced by a simple technology in the mild condition.
Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids
Joshi, Alaumy,Shaikh, Minhaj,Singh, Shubham,Rajendran, Abinaya,Mhetre, Amol,Kamat, Siddhesh S.
, p. 16953 - 16963 (2018/11/21)
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.
