33001-45-5Relevant academic research and scientific papers
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.
Non-ionic self-assembling amphiphilic polyester dendrimers as new drug delivery excipients
Sikwal, Dhiraj R.,Kalhapure, Rahul S.,Jadhav, Mahantesh,Rambharose, Sanjeev,Mocktar, Chunderika,Govender, Thirumala
, p. 14233 - 14246 (2017/03/11)
Solubility enhancement of poorly soluble antibiotics via self-assembling nano systems could be a promising approach to effectively treat bacterial infections in the current scenario of evolving resistant species. The study in this paper reports the synthesis of novel biocompatible G2 and G3 polyester amphiphilic dendrimers (ADs) (GMOA-G2-OH, GMOA-G3-OH, GMS-G2-OH and GMS-G3-OH) and their application as: (i) solubility enhancers for fusidic acid (FSD) as a model antibiotic with poor aqueous solubility and (ii) as stearic stabilizers in the preparation of solid lipid nanoparticles (SLNs). Two different series of ADs from glycerol monostearate (GMS) and glycerol monooleate (GMOA) were synthesized and their structures were confirmed employing FT-IR, NMR (1H and 13C) and HR-MS. The MTT assay confirmed their non-toxicity to mammalian cells. The critical aggregation concentration value order for ADs was GMS-G3-OH (5 × 10?6 mol l?1) ?6 mol l?1) ?5 mol l?1). All ADs formed micelles in the size range of 6.48 ± 0.04 nm to 12.38 ± 0.36 nm. At 1% w/w concentration FSD solubility enhancement in GMOA-G2-OH, GMOA-G3-OH, GMS-G2-OH and GMS-G3-OH was 43, 11, 9.1 and 6.8-fold respectively compared to water. As GMOA-G2-OH enabled the highest solubility of FSD, it was further evaluated for its antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The minimum inhibitory concentration values for FSD with and without GMOA-G2-OH against S. aureus were 0.23 μg ml?1 and 0.53 μg ml?1 respectively whereas the values were 0.23 μg ml?1 and 0.39 μg ml?1 against MRSA respectively. These results suggested that GM-OA-G2 not only enhanced the solubility but also enhanced antibacterial potency of FSD. Furthermore, these ADs showed their potential as promising pharmaceutical excipients as they acted as stearic stabilizers in the preparation of SLNs. Using these ADs stable SLNs with zeta potential value in the range of ?15.30 ± 1.44 to ?38.46 ± 3.04 were formed.
TRIACYLGLYCEROL OLIGOMERS
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Paragraph 0045, (2015/11/27)
This application relates to triacylglycerol oligomers derived from the metathesis of natural oils. These oligomers are structure controlled dimers and quatrimers, and the effect of saturation, molecular size, and positional isomerization are also described herein.
Improved enzymatic synthesis route for highly purified diacid 1,3-diacylglycerols
Wang, Xingguo,Wang, Xiaosan,Xiao, Jianhui,Zou, Wanzhen,Han, Zhengyang,Jin, Qingzhe
, p. 388 - 394 (2015/09/21)
The nutritional benefits and biological functions of diacylglycerols (DAGs) have attracted much attention regarding their synthesis. In this study, we improved the synthesis of diacid 1,3-DAGs by the enzymatic transesterification of 1-monoolein with a fatty acid vinyl ester as an acyl donor. First, 1-monoolein was prepared in 95% ethanol with Amberlyst resin as a catalyst by the cleavage of 1,2-acetonide-3-oleoylglycerol, which had been synthesized by enzymatic esterification of 1,2-acetonide glycerol with oleic acid. Second, purified 1-monoolein was reacted with vinyl palmitate in the presence of a lipase to obtain 1-oleoyl-3-palmitoylglycerol. Subsequently, the reaction conditions for the synthesis of diacid 1,3-DAGs were evaluated. Under the selected conditions, the crude mixture contained 90.6% pure 1-oleoyl-3-palmitoylglycerol. After purification by two-step crystallization, pure 1-oleoyl-3-palmitoylglycerol was obtained with a yield of 83.6%. The main innovations were the use of enzymatic transesterification to obtain highly purified diacid 1,3-DAGs instead of using chemical synthesis and the use of an irreversible reaction with a fatty acid vinyl ester as acyl donor rather than reversible reactions.
An improved method for the synthesis of 1-monoolein
Wang, Xiaosan,Jin, Qingzhe,Wang, Tong,Huang, Jianhua,Wang, Xingguo
, p. 130 - 136 (2013/10/01)
Monoacylglycerols (MAGs) are precursors for the synthesis of many active lipids and an important amphiphilic emulsifiers which are widely used in food, pharmaceutical, and cosmetic industries. In this study, we reported an improved method for the synthesis of 1-monoolein using 1,2-acetonide glycerol as starting reactant. Firstly, commercial oleic acid was purified using our previous method and then 1,2-acetonide-3-oleoylglycerol was synthesized by the esterification of 1,2-acetonide glycerol with purified oleic acid using Novozym 435 lipase as catalyst. Finally, the cleavage of unpurified 1,2-acetonide-3-oleoylglycerol in methanol was conducted to obtain 1-monoolein. The effects of reaction system, addition amount of solvent, lipase load, reaction temperature and time on 1,2-acetonide-3-oleoylglycerol content in the crude reaction mixture were investigated. Under the optimal conditions, 94.6% 1,2-acetonide-3-oleoylglycerol in crude reaction mixture was obtained. 1-Monoolein was synthesized further by cleaving unpurified 1,2-acetonide-3-oleoylglycerol in methanol at room temperature with Amberlyst-15 resin as catalyst. The cleavage reaction resulted in the formation of 76.5% 1-monoolein and 96.2% 1-monoolein was obtained at 72.8% yield after repeated recrystallization in hexane to remove nonpolar impurities and water washing to remove glycerol. The main novelties for the synthesis of 1-monoolein are the use of Novozym 435 lipase instead of chemical catalysts used in previous studies to catalyze the esterification of 1,2-acetnode glycerol with free fatty acids and scalable crystallization method used instead of column chromatography to purify 1-monoolein.
Pheromone synthesis. Part 253: Synthesis of the racemates and enantiomers of triglycerides of male Drosophila fruit flies with special emphasis on the preparation of enantiomerically pure 1-monoglycerides
Mori, Kenji
experimental part, p. 8441 - 8449 (2012/10/07)
The racemates and enantiomers of triglycerides 1aee (2,3-ditigloyloxypropyl esters of palmitic, palmitoleic, stearic, oleic, and linoleic acids) of male Drosophila fruit flies were synthesized in three steps from the racemate and enantiomers of 2,3-acetoneglycerol (2) via 1-monoglycerides 4aee derived from the above fatty acids. Appropriate conditions were established for the preparation of enantiomerically pure 1-monoglycerides 4aee, and their enantiomeric purities were determined by NMR analysis of the corresponding bis-(R)-MTPA esters.
Fatty acids residue from palm oil refining process as feedstock for lipase catalyzed monoacylglicerol production under batch and continuous flow conditions
Junior, Ivaldo I.,Flores, Marcela C.,Sutili, Felipe K.,Leite, Selma G.F.,De M. E Miranda, Leandro S.,Leal, Ivana C.R.,De Souza, Rodrigo O.M.A.
experimental part, p. 53 - 58 (2012/06/29)
Free fatty acids are used in many cases for the production of soaps, candles and assist processing of rubber products, but we believe that new process technology should be developed to produce products with higher added value. Monoacylglycerols (MAGs) are nonionic surfactant, highly hydrophobic and has been used as controlled release systems for drugs. The results presented here for the lipase-catalyzed MAG production show that both batch and continuous flow conditions can lead to the desired product in short reaction time and high yield (70-95%) but the use of packed bed reactors (PBR) shows higher efficiency when compared to batch reactors.
Evaluation of a glycerol derived biofuel by thermal analysis
Batista, Luciano N.,San Gil, Rosane A. S.,Lopes, Luciana B. R.,Soares, Vera L. P.
experimental part, p. 697 - 702 (2012/03/11)
This work describes thermal analysis evaluation of a glycerol derived compound (fatty acid esters of (2,2-dimethyl-1,3-dioxolan-4-yl) methanol) developed to work as a biofuel. Mixtures of these ketal-glyceryl esters with fatty acid methyl esters typical of soybean biodiesel were prepared and evaluated in relation to biodiesel critical thermal properties such as temperature of crystallization, thermal stability and volatilization measured by differential scanning calorimetry and thermogravimetric analysis. The volatility of the products containing fatty acid methyl esters and (2,2-dimethyl-1,3-dioxolan-4-yl) methyl esters could be predicted by thermogravimetric analyses conducted in nitrogen that avoided time consuming distillation and greatly reduced material expenditure.
Preparation of diacid 1,3-diacylglycerols
Craven, R. John,Lencki, Robert W.
experimental part, p. 1281 - 1291 (2011/08/21)
A complete methodology (including synthesis, purification and analysis) for the preparation of 1,3-DAG is described. For a successful synthesis project, the strengths and weaknesses of each particular process should be taken into account and measures taken to offset or balance potential weaknesses. To this end, we describe some of the challenges associated with: chemically and enzymatically catalyzed acylglycerol syntheses; recrystallization and flash chromatography for purification of partial acylglycerols; and thin-layer chromatography (TLC) separation of DAG. For this work, 1-MAG intermediates and subsequent diacid 1,3-DAG were prepared using non-enzymatic methods, whereas, monoacid 1,3-DAG were prepared by enzymatic methods. It was not always possible to obtain pure samples of target compounds-in recrystallizations this is due to solid solution formation and co-crystallization and in chromatographic separations it is due to co-elution of components with similar Rf. Furthermore, TLC Rf of DAG is determined by two main factors: acyl chain length and positional isomerism. Interestingly, while the role of positional isomerism is well-known, the role of acyl chain length in these separations has only recently come to light.
