Glycerol Moiety Research Articles

The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice

Acute ethanol consumption leads to the accumulation of triglycerides (TGs) in hepatocytes. The increase in lipogenesis and reduction of fatty acid oxidation are implicated as the mechanisms underlying ethanol-induced hepatic TG accumulation. Although glycerol-3-phosphate (Gro3P), formed by glycerol kinase (GYK) or glycerol-3-phosphate dehydrogenase 1 (GPD1), is also required for TG synthesis, the roles of GYK and GPD1 have been the subject of some debate. In this study, we examine (1) the expression of genes involved in Gro3P production in the liver of C57BL/6J mice in the context of hepatic TG accumulation after acute ethanol intake, and (2) the role of GPD1 in the progression of ethanol-induced fatty liver using GPD1 null mice. As a result, in C57BL/6J mice, ethanol-induced hepatic TG accumulation began within 2h and was 1.7-fold greater than that observed in the control group after 6h. The up-regulation of GPD1 began 2h after administering ethanol, and significantly increased 6h later with the concomitant escalation in the glycolytic gene expression. The incorporation of 14C-labelled glucose into TG glycerol moieties increased during the same period. On the other hand, in GPD1 null mice carrying normal GYK activity, no significant increase in hepatic TG level was observed after acute ethanol intake. In conclusion, GPD1 and glycolytic gene expression is up-regulated by ethanol, and GPD1-mediated incorporation of glucose into TG glycerol moieties together with increased lipogenesis, is suggested to play an important role in ethanol-induced hepatic TG accumulation.

Mutation of Cys242 of Human Monoacylglycerol Lipase Disrupts Balanced Hydrolysis of 1- and 2-Monoacylglycerols and Selectively Impairs Inhibitor Potency

Considerable progress has been made in recent years in developing selective, potent monoacylglycerol lipase (MAGL) inhibitors. In the investigations of measures to inhibit this enzyme, less attention has been paid to improving our understanding of its catalytic mechanisms or substrate preferences. In our study, we used site-directed mutagenesis, and we show via versatile activity assays combined with molecular modeling that Cys242 and Tyr194, the two opposing amino acid residues in the catalytic cavity of MAGL, play important roles in determining the rate and the isomer preferences of monoacylglycerol hydrolysis. In contrast to wild-type enzymes that hydrolyzed 1- and 2-monoacylglycerols at similar rates, mutation of Cys242 to alanine caused a significant reduction in overall activity (maximal velocity, Vmax), particularly skewing the balanced hydrolysis of isomers to favor the 2-isomer. Molecular modeling studies indicate that this was caused by structural features unfavorable toward 1-isomers as well as impaired recognition of OH-groups in the glycerol moiety. Direct functional involvement of Cys242 in the catalysis was found unlikely due to the remote distance from the catalytic serine. Unlike C242A, mutation of Tyr194 did not bias the hydrolysis of 1- and 2-monoacylglycerols but significantly compromised overall activity. Finally, mutation of Cys242 was also found to impair inhibition of MAGL, especially that by fluorophosphonate derivatives (13- to 63-fold reduction in potency). Taken together, this study provides new experimental and modeling insights into the molecular mechanisms of MAGL-catalyzed hydrolysis of the primary endocannabinoid 2-arachidonoylglycerol and related monoacylglycerols.

A coumarinylaldoxime as a specific sensor for Cu2+ and its biological application

In this Letter we present a new probe, (E)-7-(diethylamino)-2-oxo-2H-chromene-3-carbaldehyde oxime (JB), which can detect Cu2+ ions in HEPES buffer under physiological conditions. Benesi–Hildebrand and Job plots demonstrate that the stoichiometry of the Cu2+ complex formed is 2:1. Possible interference with other analytes was examined, and the decrease of the fluorescence of JB at 510nm when it reacts with Cu2+ was shown to be highly selective. This probe accumulates in the plasmalemma of human neuroblastoma SH-SY5Y cells. Molecular dynamics (MD) simulations revealed that JB interacts with the lipid bilayer at the level of the glycerol moieties.

Structure Activity Relationships of N-linked and Diglycosylated Glucosamine-Based Antitumor Glycerolipids

1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-d-glucopyranosyl)-sn-glycerol (1) was previously reported to show potent in vitro antitumor activity on a range of cancer cell lines derived from breast, pancreas and prostate cancer. This compound was not toxic to mice and was inactive against breast tumor xenografts in mice. This inactivity was attributed to hydrolysis of the glycosidic linkage by glycosidases. Here three N-linked (glycosylamide) analogs 2–4, one triazole-linked analog 5 of 1 as well as two diglycosylated analogs 6 and 7 with different stereochemistry at the C2-position of the glycerol moiety were synthesized and their antitumor activity against breast (JIMT-1, BT-474, MDA-MB-231), pancreas (MiaPaCa2) and prostrate (DU145, PC3) cancer cell lines was determined. The diglycosylated analogs 1-O-hexadecyl-2(R)-, 3-O-di-(2'-amino-2'-deoxy-β-d-glucopyranosyl)-sn-glycerol (7) and the 1:1 diastereomeric mixture of 1-O-hexadecyl-2(R/S), 3-O-di-(2'-amino-2'-deoxy-β-d-glucopyranosyl)-sn-glycerol (6) showed the most potent cytotoxic activity at CC50 values of 17.5 µM against PC3 cell lines. The replacement of the O-glycosidic linkage by a glycosylamide or a glycosyltriazole linkage showed little or no activity at highest concentration tested (30 µM), whereas the replacement of the glycerol moiety by triazole resulted in CC50 values in the range of 20 to 30 µM. In conclusion, the replacement of the O-glycosidic linkage by an N-glycosidic linkage or triazole-linkage resulted in about a two to three fold loss in activity, whereas the replacement of the methoxy group on the glycerol backbone by a second glucosamine moiety did not improve the activity. The stereochemistry at the C2-position of the glycero backbone has minimal effect on the anticancer activities of these diglycosylated analogs.

Geranylgeranyl Reductase and Ferredoxin from Methanosarcina acetivorans Are Required for the Synthesis of Fully Reduced Archaeal Membrane Lipid in Escherichia coli Cells

Archaea produce membrane lipids that typically possess fully saturated isoprenoid hydrocarbon chains attached to the glycerol moiety via ether bonds. They are functionally similar to, but structurally and biosynthetically distinct from, the fatty acid-based membrane lipids of bacteria and eukaryotes. It is believed that the characteristic lipid structure helps archaea survive under severe conditions such as extremely low or high pH, high salt concentrations, and/or high temperatures. We detail here the first successful production of an intact archaeal membrane lipid, which has fully saturated isoprenoid chains, in bacterial cells. The introduction of six phospholipid biosynthetic genes from a methanogenic archaeon, Methanosarcina acetivorans, in Escherichia coli enabled the host bacterium to synthesize the archaeal lipid, i.e., diphytanylglyceryl phosphoglycerol, while a glycerol modification of the phosphate group was probably catalyzed by endogenous E. coli enzymes. Reduction of the isoprenoid chains occurred only when archaeal ferredoxin was expressed with geranylgeranyl reductase, suggesting the role of ferredoxin as a specific electron donor for the reductase. This report is the first identification of a physiological reducer for archaeal geranylgeranyl reductase. On the other hand, geranylgeranyl reductase from the thermoacidophilic archaeon Sulfolobus acidocaldarius could, by itself, replace both its orthologue and ferredoxin from M. acetivorans, which indicated that an endogenous redox system of E. coli reduced the enzyme.

The turnover of glycerol and acyl moieties of cardiolipin

The dynamical behavior of mitochondria has attracted much attention, but little is known about the dynamics of mitochondrial lipids, specifically cardiolipin (CL). Here, we estimated the turnover of select molecular species of CL in mammalian cell cultures and compared it to the turnover of other lipids, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol. Cells were labeled with myristic acid, 9,10-2H2-oleic acid, or d-[U-13C6]-glucose and analyzed by mass spectrometry at different time points of pulse-chase experiments. The turnover of glycerol groups was monitored by specific isotopologues that carried 13C primarily in the glycerol carbons, whereas the turnover of acyl groups was monitored by molecular species that carried myristoyl or 2H2-oleoyl groups. We found that the turnover of CL, but not of mitochondrial PC and PE, was substantially slower than the turnover of other cellular phospholipids. In dioleoyl-PC and dioleoyl-PE, the acyl turnover was faster than the glycerol turnover, indicating continuous deacylation and reacylation of the oleoyl residues. In contrast, the acyl turnover was similar to the glycerol turnover in tetraoleoyl-CL, suggesting that oleoyl remodeling did not take place continuously in endogenous CL. We conclude that CL, once assembled in mitochondrial membranes, remains largely inert to degradation and acyl remodeling.

Anti-microfouling properties of compounds isolated from several Mediterranean Dictyota spp.

Brown algae of the genus Dictyota are widespread around the world and are common along the coasts of the Mediterranean Sea. These marine organisms keep their surface relatively free from biofouling and are known for their ability to produce a wide array of bioactive compounds, mostly diterpenes, whose ecological functions are not clearly defined. In this study, an evaluation of the chemodiversity of the Dictyota genus was conducted on three samples, harvested on both NW and SW Mediterranean coasts (France and Algeria, respectively). Ten compounds were purified from the organic extracts of these samples; their chemical structures were elucidated by 1D and 2D NMR spectroscopy and were compared with literature data. Among them, three new diterpenes [one dolabellane (1), one xenicane (2), and one prenylated guaiane (3)] were characterized together with five previously described compounds [3,4-epoxy-14-oxo-7,18-dolabelladiene (4), acetoxycrenulide (5), dictyol E (6), 10,18-dihydroxydolabella-2,7-diene (7), and 10-acetoxy-18-hydroxydolabella-2,7-diene (8)]. In addition, the occurrence of two known glycerol derivatives [1-Ο-octadecenoylglycerol (9) and sn-3-Ο-(geranylgeranyl)glycerol (10)] was also determined. Some of the isolated compounds (4–6 and 8–10) were screened for their potential to prevent the adhesion of three bacterial strains isolated from marine biofilms in comparison with four commercial antifoulants (TBTO, Zineb, ZnPT, and CuPT): those bearing a glycerol moiety (compounds 9 and 10) exhibited the strongest anti-adhesion effects, whatever the strain, and with a moderate toxicity. Thus, these chemical structures should be further explored for both their putative involvement in keeping the algal surface free of biofouling and the development of effective and environmentally benign antifoulants.

Conformational Plasticity and Ligand Binding of Bacterial Monoacylglycerol Lipase

Monoacylglycerol lipases (MGLs) play an important role in lipid catabolism across all kingdoms of life by catalyzing the release of free fatty acids from monoacylglycerols. The three-dimensional structures of human and a bacterial MGL were determined only recently as the first members of this lipase family. In addition to the α/β-hydrolase core, they showed unexpected structural similarities even in the cap region. Nevertheless, the structural basis for substrate binding and conformational changes of MGLs is poorly understood. Here, we present a comprehensive study of five crystal structures of MGL from Bacillus sp. H257 in its free form and in complex with different substrate analogs and the natural substrate 1-lauroylglycerol. The occurrence of different conformations reveals a high degree of conformational plasticity of the cap region. We identify a specific residue, Ile-145, that might act as a gatekeeper restricting access to the binding site. Site-directed mutagenesis of Ile-145 leads to significantly reduced hydrolase activity. Bacterial MGLs in complex with 1-lauroylglycerol, myristoyl, palmitoyl, and stearoyl substrate analogs enable identification of the binding sites for the alkyl chain and the glycerol moiety of the natural ligand. They also provide snapshots of the hydrolytic reaction of a bacterial MGL at different stages. The alkyl chains are buried in a hydrophobic tunnel in an extended conformation. Binding of the glycerol moiety is mediated via Glu-156 and water molecules. Analysis of the structural features responsible for cap plasticity and the binding modes of the ligands suggests conservation of these features also in human MGL.

The supramolecular structure is decisive for the immunostimulatory properties of synthetic analogues of a mycobacterial lipid in vitro

Identification of new vaccine adjuvants with immunopotentiating properties commonly involves in vitro evaluations of candidate compounds for their ability to stimulate cells of the immune system. Subsequent elaborate experiments are then performed on only the positive candidates. Here we show how this strategy may miss good candidates due to context-dependent supramolecular characteristics of the candidate compounds, since both a specific molecular structure and the correct presentation of specific parts of the compounds are required for successful stimulation of the cells. Nevertheless, the supramolecular structure is rarely evaluated although changes in this structure may have a drastic impact on the presentation of the compounds to the cells. Synthetic analogues of the mycobacterial cell wall lipid monomycoloyl glycerol (MMG) possess immunopotentiating properties, but their biophysical characteristics are largely unresolved and the structural features determining their immunoactivating properties have been poorly explored. In the present study, we demonstrate that the immunostimulatory activity in vitro correlates with the supramolecular characteristics of the self-assembled MMG nanostructures. Thus, a series of MMG analogues displaying different stereochemistry in the hydrophobic moiety and the polar headgroup were designed and synthesized with different alkyl chain lengths. Stimulation of human monocyte-derived dendritic cells in vitro was clearly dependent on the stereochemistry of the hydrophobic part and on the alkyl chain length but not on the stereochemistry of the hydrophilic glycerol moiety. Small-angle X-ray scattering (SAXS) analysis showed that the immunoactivating analogues self-assembled into lamellar phases whereas the biologically inert analogues adopted inverse hexagonal phases. Langmuir monolayers confirmed that analogues with opposite lipid acid configurations displayed different packing modes. These data demonstrate that the biophysical properties and the lipid molecular structure are major determinants for the ability of the MMG analogues to activate antigen-presenting cells. Our findings emphasize the importance of investigating the biophysical and structural properties when assessing the effect of adjuvants in vitro.

Design, synthesis and cellular dynamics studies in membranes of a new coumarin-based “turn-off” fluorescent probe selective for Fe2+

A new coumarin-based ‘turn-off’ fluorescent probe, 7-(diethylamino)-N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-oxo-2H-chromene-3-carboxamide (AGD) was synthesized. This compound is highly selective for ferrous ions (Fe2+) and can reversibly detect them in aqueous medium. The probe localizes to the cell membrane in living cells, where it can detect changes in Fe2+ concentration. Molecular dynamics (MD) simulations indicate that AGD interacts with the lipid bilayer at the level of the glycerol moieties.

Selective reduction of bis(monoacylglycero)phosphate ameliorates the storage burden in a THP-1 macrophage model of Gaucher disease

Bis(monoacylglycero)phosphate (BMP) assists lysosomal function by facilitating interaction of hydrolases and activator proteins with sphingolipid substrates. Impaired lysosomal degradation of the sphingolipid glucosylceramide (GC) occurs in Gaucher disease due to an inherited deficiency of acid β-glucosidase, with secondary BMP alterations. We investigated the nature of BMP accumulation and whether its correction reduced the storage burden in a THP-1 macrophage model of Gaucher disease. Using sucrose gradients and detergent solubility, 98% of BMP resided in the detergent-soluble membranes (DSM) rather than in the detergent-resistant membranes (DRM) where 73% of GC predominated. There was a 2-fold widespread elevation in BMP, including the saturated, mono- and polyunsaturated species. Linoleic acid in the culture media selectively reduced BMP from 4.2 nmol/mg to 0.49 nmol/mg (except 18:1/18:2) and prevented up to one third of GC, dihexosylceramide (DHC), and trihexosylceramide (THC) from accumulating. The 2-fold reduction in these sphingolipids occurred only in the DRM and did not reduce 18:1/16:0. However, once GC had accumulated, linoleic acid could not reverse it, DHC, or THC, despite effectively reducing BMP. These results imply a causative link for BMP in the pathobiology of Gaucher disease and demonstrate that linoleic acid can shield the cell from excessive substrate accumulation.

Comparison of postprandial lipaemia between native and palm random esterified acid oils in two different monogastric species (dogs and broiler chickens)

It has been reported that applying a chemical reesterification process to a native fat results in a new fat source with different physicochemical properties due to their different fatty acid (FA) positional distribution within the glycerol moiety and their different proportions of mono (MAG)-, di (DAG)- and triacylglycerides (TAG). Thus, this reesterification could affect fat digestion, absorption and metabolism; and this effect could vary among species given their differences in fat metabolism. The aim of this study was to compare the effect of feeding two different random esterified acid oils (REAO), presenting different MAG, DAG and TAG proportions, with their corresponding native oil on postprandial lipaemia in broiler chickens and dogs. For this purpose, 18 dogs and 54 broiler chickens were fed a basal diet supplemented with palm native oil, palm REAO low MAG or palm REAO high MAG. The inclusion level of the oils was 10% of the diet in dogs and 6% in broiler chickens. Serum postprandial TAG concentration (mg/dl) after feeding a single meal was measured at different time points during 12 h in dogs and 3 h in chickens. Although fasting serum TAG concentration values were similar for both species (47 ± 2.4 mg/dl for dogs and 44 ± 3.0 mg/dl for broilers; p = 0.522), postprandial TAG concentrations tended to be higher in broilers than in dogs (p = 0.058). Treatment had no effect on TAG concentration at any time point in any species (p = 0.768 for dogs, p = 0.947 for broilers). However, the postprandial TAG curves were very different between species; in broiler chickens, TAG concentration returned to the fasting values 3 h after feeding while in dogs, the TAG concentration still had not returned to basal levels 12 h after feeding.

Metabolism of Glycerol, Glucose, and Lactate in the Citric Acid Cycle Prior to Incorporation into Hepatic Acylglycerols

During hepatic lipogenesis, the glycerol backbone of acylglycerols originates from one of three sources: glucose, glycerol, or substrates passing through the citric acid cycle via glyceroneogenesis. The relative contribution of each substrate source to glycerol in rat liver acylglycerols was determined using (13)C-enriched substrates and NMR. Animals received a fixed mixture of glucose, glycerol, and lactate; one group received [U-(13)C6]glucose, another received [U-(13)C3]glycerol, and the third received [U-(13)C3]lactate. After 3 h, the livers were harvested to extract fats, and the glycerol moiety from hydrolyzed acylglycerols was analyzed by (13)C NMR. In either fed or fasted animals, glucose and glycerol provided the majority of the glycerol backbone carbons, whereas the contribution of lactate was small. In fed animals, glucose contributed >50% of the total newly synthesized glycerol backbone, and 35% of this contribution occurred after glucose had passed through the citric acid cycle. By comparison, the glycerol contribution was ~40%, and of this, 17% of the exogenous glycerol passed first through the cycle. In fasted animals, exogenous glycerol became the major contributor to acylglycerols. The contribution from exogenous lactate did increase in fasted animals, but its overall contribution remained small. The contributions of glucose and glycerol that had passed through the citric acid cycle first increased in fasted animals from 35 to 71% for glucose and from 17 to 24% for glycerol. Thus, a substantial fraction from both substrate sources passed through the cycle prior to incorporation into the glycerol moiety of acylglycerols in the liver.

Process development and simulation of glycerol-free biofuel from canola oil and dimethyl carbonate

Biofuels, especially biodiesel, have become commonplace over the last couple of decades. The conventional transesterification process used for biodiesel production leaves manufacturers with a byproduct, glycerol, that is of low value. Dimethyl carbonate has been studied as an alternate methylating agent to methanol and alters the chemistry such that glycerol is not formed. Triazabicyclodecene was chosen as the catalyst due to its ability to easily ionize the dimethyl carbonate and ease of separation post reaction.This paper reports on the development of specific processing steps to convert canola oil to FAMEs and fatty acid glycerol carbonate (FAGCs) compounds. The process flow diagram was developed using Aspen Plus simulation software and verified through laboratory testing. Process conditions were adjusted until a glycerol-free biofuel was produced that meets the ASTM D6751 standard for biodiesel. By utilizing the glycerol moiety within the final product, about 9.7% increase (by mass) of biofuel was obtained compared to the traditional methanol synthesis route. Glycerol carbonate and glycerol dicarbonate were formed as byproducts but were in low concentrations. These results reveal the potential of using dimethyl carbonate as a replacement for methanol to produce an acceptable, more environmentally friendly biofuel.

Structural studies on archaeal phytanyl-ether lipids isolated from membranes of extreme halophiles by linear ion-trap multiple-stage tandem mass spectrometry with electrospray ionization

The structures of archaeal glycerophospholipids and glycolipids are unique in that they consist of phytanyl substituents ether linked to the glycerol backbone, imparting stability to the molecules. In this contribution, we described multiple-stage linear ion-trap combined with high resolution mass spectrometry toward structural characterization of this lipid family desorbed as lithiated adduct ions or as the [M−H]− and [M−2H]2− ions by ESI. MSn on various forms of the lithiated adduct ions yielded rich structurally informative ions leading to complete structure identification of this lipid family, including the location of the methyl branches of the phytanyl chain. By contrast, structural information deriving from MSn on the [M−H]− and [M−2H]2− ions is not complete. The fragmentation pathways in an ion-trap, including unusual internal loss of glycerol moiety and internal loss of hexose found for this lipid family were proposed. This mass spectrometric approach provides a simple tool to facilitate confident characterization of this unique lipid family.

Synthesis and biological activity of phosphoglycolipids from Thermus thermophilus

An extreme thermophile, Thermus thermophilus, has very unique glycolipids on the cell surface. The acidic immunostimulatory phosphoglycolipid of T. thermophilus was synthesized for the first time, with newly developed glycosylation methods using 3-nitropyridyl (3NPy) and 4,6-dimethoxy-1,3,5-triazin-2-yl (DMT) glycosides as glycosyl donors. The analogues of the phosphoglycolipid, which include a diastereomer possessing the opposite configuration at the diacyl glycerol moiety, were also synthesized. The biological activities of the synthesized compounds were elucidated with cytokine inductions (IL-6 and TNF-α). A synthetic phosphoglycolipid with a natural-type diacyl glycerol configuration showed apparent immunostimulatory activity, whereas its diastereomer did not. The present study revealed that the configuration at the diacyl glycerol moiety of the phosphoglycolipids is important for immunostimulation, suggesting the existence of the particular receptor/recognizing protein that can recognize the stereochemistry of the glycerol part.

Assessing production of the ubiquitous archaeal diglycosyl tetraether lipids in marine subsurface sediment using intramolecular stable isotope probing

The membrane lipids diglycosyl-glycerol dibiphytanyl glycerol tetraethers (2G-GDGTs) in marine subsurface sediments are believed to originate from uncultivated benthic archaea, yet the production of 2G-GDGTs from subseafloor samples has not been demonstrated in vitro. In order to validate sedimentary biosynthesis of 2G-GDGTs, we performed a stable carbon isotope probing experiment on a subseafloor sample with six different (13) C-labelled substrates (bicarbonate, methane, acetate, leucine, glucose and Spirulina platensis biomass). After 468 days of anoxic incubation, only glucose and S. platensis resulted in label uptake in lipid moieties of 2G-GDGTs, indicating incorporation of carbon from these organic substrates. The hydrophobic moieties of 2G-GDGTs showed minimal label incorporation, with up to 4‰ (13) C enrichment detected in crenarchaeol-derived tricyclic biphytane from the S. platensis-supplemented slurries. The 2G-GDGT-derived glucose or glycerol moieties also showed (13) C incorporation (Δδ(13) C = 18-38‰) in the incubations with glucose or S. platensis, consistent with a lipid salvage mechanism utilized by marine benthic archaea to produce new 2G-GDGTs. The production rates were nevertheless rather slow, even when labile organic matter was supplied. The 2G-GDGT turnover times of 1700-20,500 years were much longer than those estimated for subseafloor microbial communities, implying that sedimentary 2G-GDGTs as biomarkers of benthic archaea are cumulative records of past and present generations.

Characterization of Polyglycerol Polyricinoleate Formulations Using NMR Spectroscopy, Mass Spectrometry and Dynamic Light Scattering

AbstractThree different analytical techniques, namely NMR spectroscopy, mass spectrometry and dynamic light scattering, were used to unravel the structure and morphology of polyglycerol polyricinoleate (PGPR). This material is used as an emulsifier in the preparation of chocolate and other confectionary products. The use of 1D and 2D NMR techniques led to the distinction of two separate entities in commercial ricinoleic acid (RA) and PGPR samples, namely the monomeric and oligomeric RA (estolides). 1H and 13C spectra of PGPR confirmed the presence of polyglycerol moieties of various lengths being esterified by RA and estolides and to a lesser extent by oleic and linoleic acids. 13C‐NMR DOSY experiments demonstrated the occurrence of several species in PGPR. Electrospray Ionization and tandem Mass Spectrometry succeeded in identifying the presence of over 30 glycerol/polyglycerol species containing n glycerol moieties with n = 1–6 esterified by monomeric and oligomeric RA molecules. Dynamic light scattering contributed to the characterization of PGPR morphology. The PGPR mixture contains relatively small‐sized entities (monomers, dimmers, trimmers) and larger aggregates resulted from chain association. The percentage of larger aggregates is minimal compared to small‐sized species.

Activation of n-3 polyunsaturated fatty acids as oxime esters: a novel approach for their exclusive incorporation into the primary alcoholic positions of the glycerol moiety by lipase

A novel approach has been developed for activating the highly bioactive long-chain n-3 polyunsaturated fatty acids EPA and DHA as oxime esters and incorporating them exclusively to the end-positions of glycerol and enantiopure 1-O-alkylglycerols. The Candida antarctica lipase B was observed to display a superb regioselectivity when using the acetoxime esters of EPA and DHA as acyldonors under mild condition to keep acyl-migration side-reaction under complete control. Regiopure 1,3-diacylglycerols, 1-O-alkyl-3-acyl-sn-glycerols and their antipodes possessing EPA and DHA were afforded in very high purity and yields.

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens.

Mycoplasma fermentans possesses unique α-glycolipid antigens (GGPL-I and GGPL-III) at the cytoplasm membrane, which carry a phosphocholine group at the sugar primary (6-OH) position. This paper describes a practical synthetic pathway to a GGPL-I homologue (C16:0) and its diastereomer, in which our one-pot α-glycosylation method was effectively applied. The synthetic GGPL-I isomers were characterized with 1H NMR spectroscopy to determine the equilibrium among the three conformers (gg, gt, tg) at the acyclic glycerol moiety. The natural GGPL-I isomer was found to prefer gt (54%) and gg (39%) conformers around the lipid tail, while adopting all of the three conformers with equal probability around the sugar position. This property was very close to what we have observed with respect to the conformation of phosphatidylcholine (DPPC), suggesting that the Mycoplasma glycolipids GGPLs may constitute the cytoplasm fluid membrane together with ubiquitous phospholipids, without inducing stereochemical stress.