- Regulation of mitochondrial ceramide distribution by members of the BCL-2 family
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Apoptosis is an intricately regulated cellular process that proceeds through different cell type- and signaldependent pathways. In the mitochondrial apoptotic program, mitochondrial outer membrane permeabilization by BCL-2 proteins leads to the release of apoptogenic factors, caspase activation, and cell death. In addition to protein components of the mitochondrial apoptotic machinery, an interesting role for lipids and lipid metabolism in BCL-2 family-regulated apoptosis is also emerging. We used a comparative lipidomics approach to uncover alterations in lipid profi le in the absence of the proapoptotic proteins BAX and BAK in mouse embryonic fi broblasts (MEFs). We detected over 1,000 ions in these experiments and found changes in an ion with an m/z of 534.49. Structural elucidation of this ion through tandem mass spectrometry revealed that this molecule is a ceramide with a 16-carbon N-acyl chain and sphingadiene backbone (d18:2/16:0 ceramide). Targeted LC/MS analysis revealed elevated levels of additional sphingadiene-containing ceramides (d18:2-Cers) in BAX, BAK-double knockout MEFs. Elevated d18:2-Cers are also found in immortalized baby mouse kidney epithelial cells lacking BAX and BAK. These results support the existence of a distinct biochemical pathway for regulating ceramides with different backbone structures and suggest that sphingadiene-containing ceramides may have functions that are distinct from the more common sphingosinecontaining species .
- Zhang, Tejia,Barclay, Lauren,Walensky, Loren D.,Saghatelian, Alan
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Read Online
- Antiproliferative 3-deoxysphingomyelin analogs: Design, synthesis, biological evaluation and molecular docking of pyrrolidine-based 3-deoxysphingomyelin analogs as anticancer agents
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Sphingomyelins and glycerophospholipids are structurally related phospholipids. Nevertheless, glycerophospholipids analogs are known as antitumor agents while sphingomyelin analogs were reported as cytoprotective agents. Herein, we have addressed the development of 3-deoxysphingomyelin analogs as cytotoxic agents possessing modified sphingobases. Thus, pyrrolidine-based 3-deoxysphingomyelin analogs were synthesized and evaluated against a panel of cell lines representing four major types of cancers. Compounds 3d, 4d and 6d elicited better GI50 values than the FDA approved drug miltefosine. Investigation of their impact on Akt phosphorylation as a possible mechanism for the antiproliferative activity of this class of compounds revealed that these compounds might elicit a concentration-dependent mechanism via inhibition of Akt phosphorylation at the lower concentration. Molecular docking predicted their binding modes to Akt to involve polar head binding to the Pleckstrin homology domain and hydrophobic tail extension into a hydrophobic pocket connecting the Pleckstrin homology domain and the kinase domain. As a whole, the described work suggests compounds 3d, 4d and 6d as promising pyrrolidine-based 3-deoxysphingomyelin analogs for development of novel cancer therapies.
- Hassan, Ahmed H.E.,Park, Hye Rim,Yoon, Yoon Mi,Kim, Hye In,Yoo, Sung Yeun,Lee, Kun Won,Lee, Yong Sup
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p. 444 - 455
(2019/01/03)
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- N-Acylated amino acid methyl esters from marine Roseobacter group bacteria
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Bacteria of the Roseobacter group (Rhodobacteraceae) are important members of many marine ecosystems. Similar to other Gram-negative bacteria many roseobacters produce N-acylhomoserine lactones (AHLs) for communication by quorum sensing systems. AHLs regulate different traits like cell differentiation or antibiotic production. Related N-acylalanine methyl esters (NAMEs) have been reported as well, but so far only from Roseovarius tolerans EL-164. While screening various roseobacters isolated from macroalgae we encountered four strains, Roseovarius sp. D12_1.68, Loktanella sp. F13, F14 and D3 that produced new derivatives and analogs of NAMEs, namely N-acyl-2-aminobutyric acid methyl esters (NABME), N-acylglycine methyl esters (NAGME), N-acylvaline methyl esters (NAVME), as well as for the first time a methyl-branched NAME, N-(13-methyltetradecanoyl)alanine methyl ester. These compounds were detected by GC–MS analysis, and structural proposals were derived from the mass spectra and by derivatization. Verification of compound structures was performed by synthesis. NABMEs, NAVMEs and NAGMEs are produced in low amounts only, making mass spectrometry the method of choice for their detection. The analysis of both EI and ESI mass spectra revealed fragmentation patterns helpful for the detection of similar compounds derived from other amino acids. Some of these compounds showed antimicrobial activity. The structural similarity of N-acylated amino acid methyl esters and similar lipophilicity to AHLs might indicate a yet unknown function as signalling compounds in the ecology of these bacteria, although their singular occurrence is in strong contrast to the common occurrence of AHLs. Obviously the structural motif is not restricted to Roseovarius spp. and occurs also in other genera.
- Bruns, Hilke,Ziesche, Lisa,Taniwal, Nargis Khakin,Wolter, Laura,Brinkhoff, Thorsten,Herrmann, Jennifer,Müller, Rolf,Schulz, Stefan
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supporting information
p. 2964 - 2973
(2018/12/13)
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- Ceramide compound, a process of preparing the ceramide compound, an intermediate compound and a process of preparing the intermediate compound
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The structural properties of naturally occurring ceramide specification disclosure ceramide like compounds are disclosed. Hydroxy fatty acids (ω - hydroxy fatty acid) is provided end (to alcohol) i.e., ω - alkyl group such as hydroxy group is the group which will know various partially defect number [...] disclosure method is the natural ceramide like structure compounds are disclosed. Using the same, and the shortcomings of natural ceramide list price is expensive, and maintains the also obtain, number and sanitary door number can be overcome and purity of product, lactic effective natural ceramide constrictive forces over properties. (by machine translation)
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Paragraph 0189
(2017/10/31)
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- N-acylated alanine methyl esters (NAMEs) from Roseovarius tolerans, structural analogs of quorum-sensing autoinducers, N-acylhomoserine lactones
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The Roseobacter clade is one of the most important bacteria group living in the ocean. Liquid cultures of Roseovarius tolerans EL 164 were investigated for the production of autoinducers such as N-acylhomoserine lactones (AHLs) and other secondary metabolites. The XAD extracts were analyzed by GC/MS. Two AHLs, Z7-C14: 1-homoserine lactone (HSL) and C15: 1-HSL, were identified. Additionally, the extract contained five compounds with molecular-ion peaks at m/z 104, 145, and 158, thus exhibiting mass spectra similar to those of AHLs with corresponding peaks at m/z 102, 143, and 156. Isolation of the main compound by column chromatography, NMR analysis, dimethyl disulfide derivatization for the determination of the location of the CiC bond and finally synthesis of the compound with the proposed structure confirmed the compound to be (Z)-N-(hexadec-9-enoyl)alanine methyl ester. Four additional minor compounds were identified as C14: 0-, C15: 0-, C16: 0-, and C17: 1-N-acylated alanine methyl esters (NAMEs). All NAMEs have not been described from natural sources before. A BLASTp search showed the presence of AHL-producing luxI genes, but no homologous genes potentially responsible for the structurally closely related NAMEs were found. The involvement of the NAMEs in chemical communication processes of the bacteria is discussed. Copyright
- Bruns, Hilke,Thiel, Verena,Voget, Sonja,Patzelt, Diana,Daniel, Rolf,Wagner-Doebler, Irene,Schulz, Stefan
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p. 1559 - 1573
(2013/10/21)
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- Lizard epidermal gland secretions. II. Chemical characterization of the generation gland secretion of the sungazer, cordylus giganteus
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In lizards, the epidermal glands of the femoral and precloacal regions are involved in the production of semiochemicals. In addition to its femoral glands, the giant girdled lizard, or sungazer, Cordylus giganteus, which is endemic to South Africa, has generation glands as an additional potential source of semiochemicals. These epidermal glands are described as glandular scales that overlay the femoral glands and are included in the normal epidermal profile located in the femoral (thigh) and anterior antebrachial (fore-leg) regions of the male sungazer. GC-MS analysis of the generation gland secretions and the trimethylsilyl derivatives of some of the steroidal constituents was employed to identify 59 constituents, including alkenes, carboxylic acids, alcohols, ketones, aldehydes, esters, amides, nitriles, and steroids. The quantitative differences of the volatile constituents of the fore- and hind-leg generation glands were compared between individuals. This is the first report on the chemical composition of generation glandular material of lizards.
- Louw, Stefan,Burger, Ben V.,Le Roux, Maritha,Van Wyk, Johannes H.
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supporting information; experimental part
p. 1364 - 1369
(2011/08/09)
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- Improved LC-MS method for the determination of fatty acids in red blood cells by LC-orbitrap MS
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We report a new method for fast and sensitive analyses of biologically relevant fatty acids (FAs) in red blood cells (RBC) by liquid chromatography mass spectrometry (LC-MS). A new chemical derivatization approach was developed forming picolylamides from FAs in a quantitative reaction. Fourteen derivatized FA standards, including saturated and unsaturated FAs from C14 to C22, were efficiently separated within 15 min. In addition, the use of a recently introduced benchtop orbitrap mass spectrometer under positive electrospray ionization (ESI) full scan mode showed a 2-10-fold improvement in sensitivity compared with a conventional tandem MS method, with a limit of detection in the low femtomole range for saturated and unsaturated FAs. The developed method was applied to determine FA concentrations in RBC with intra- and interday coefficients of variation below 10%.
- Li, Xingnan,Franke, Adrian A.
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experimental part
p. 3192 - 3198
(2011/11/04)
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- Creatine-fatty acids
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The present invention describes compounds produced from a creatine molecule and a fatty acid molecule. The compounds being in the form of creatine-fatty compounds bound by an amide linkage, or mixtures thereof produced by reacting creatine or derivatives thereof with an appropriate fatty acid in the presence of dichloromethane and a pyridine catalyst, previously reacted with a thionyl halide. The administration of such molecules provides supplemental creatine with enhanced bioavailability and the additional benefits conferred by the specific fatty acid.
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Page/Page column 10
(2008/06/13)
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- CREATINE-FATTY ACIDS
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The present invention describes compounds produced from a creatine molecule and a fatty acid molecule. The compounds being in the form of creatine-fatty compounds bound by an amide linkage, or mixtures thereof produced by reacting creatine or derivatives thereof with an appropriate fatty acid in the presence of dichloromethane and a pyridine catalyst, previously reacted with a thionyl halide. The administration of such molecules provides supplemental creatine with enhanced bioavailability and the additional benefits conferred by the specific fatty acid. Formula (I)
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Page/Page column 10-11
(2008/12/08)
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- Host-recognizing kairomones for parasitic wasp, Anisopteromalus calandrae, from larvae of azuki bean weevil, Callosobruchus chinensis.
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Host-recognizing kairomones for the stinging behavior of the parasitic wasp, Anisopteromalus calandrae, were identified on host azuki bean weevil larvae, Callosobruchus chinensis (L.). The kairomones were extracted with acetone from Chinese green beans, from which emerged wasps and host weevils had been removed. The kairomones are a mixture of triacylglycerols and fatty acids, each of which is separately active, and with no observable synergistic effect between them. These compounds are known to be constituents of an oviposition-marking pheromone of host azuki bean weevils. However, they differ from the previously reported saturated hydrocarbons and diacylglycerols of the kairomone that another parasitic wasp, Dinarmus basalis, uses for the host recognition of C. chinensis. Thus, A. calandrae and D. basalis selectively utilize different constituents of the oviposition-marking pheromone of C. chinensis as host-recognizing kairomones.
- Onodera, Junko,Matsuyama, Shigeru,Suzuki, Takahisa,Fujii, Koichi
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p. 1209 - 1220
(2007/10/03)
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- Vanilloids. 1. Analogs of Capsaicin with Antinociceptive and Antiinflammatory Activity
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As part of a program to establish structure-activity relationships for vanilloids, analogs of the pungent principle capsaicin, the alkyl chain portion the parent structure (and related compounds derived from homovanillic acid) was varied.In antinociceptive and antiinflammatory assays (rat and mouse hot plate and croton oil-inflamed mouse ear), compounds with widely varying alkyl chain structures were active.Short-chain compounds were active by systemic administration in the assays mentioned above but they retained the high pungency and acute toxicity characteristic of capsaicin.In contrast, the long chain cis-unsaturates, NE-19550 (vanillyloleamide) and NE-28345 (oleylhomovanillamide), were orally active, less pungent, and less acutely toxic than capsaicin.The potential of these compounds as antiinflammatory/analgesic agents is discussed in light of recent data on the mechanism of action of vanilloids on sensory nerve fibers.
- Janusz, John M.,Buckwalter, Brian L.,Young, Patricia A.,LaHann, Thomas R.,Farmer, Ralph W.,et al.
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p. 2595 - 2604
(2007/10/02)
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