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• W1980355616 endingPage "504" @default.
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• W1980355616 abstract "Advances in lipid separation methods and mass spectrometry technologies allow the fine characterization of the lipidome of parasites, ranging from unicellular protists to worms, which cause threatening infections in vertebrates, including humans. Specific lipid structures or lipid metabolic pathways can inspire the development of novel antiparasitic drugs. Changes in the lipid balance in membranes of parasites can also provide clues on the dynamics of drugs and some mechanisms of drug resistance. This review highlights recent trends in parasite lipidomics, combined with functional analyses, for the discovery of novel targets and the development of novel drugs. Advances in lipid separation methods and mass spectrometry technologies allow the fine characterization of the lipidome of parasites, ranging from unicellular protists to worms, which cause threatening infections in vertebrates, including humans. Specific lipid structures or lipid metabolic pathways can inspire the development of novel antiparasitic drugs. Changes in the lipid balance in membranes of parasites can also provide clues on the dynamics of drugs and some mechanisms of drug resistance. This review highlights recent trends in parasite lipidomics, combined with functional analyses, for the discovery of novel targets and the development of novel drugs. technique used in mass spectrometry (MS) to produce ions at atmospheric pressure. APCI is adapted to the ionization of non-polar (e.g. triacylglycerol) to very polar molecules, with a molecular weight ranging from around 50 to 1000 kDa. technique used in MS to produce ions after exposure of analytes to UV light photons. APPI is adapted to the ionization of non-polar (e.g. triacylglycerol) to polar molecules, with a molecular weight ranging from around 100 to 2000 kDa. in vitro reconstitution of a biological membrane, based on the self-organization of polar lipids in mono- or bilayers. technique used in MS to produce ions, generating ions in a gas phase without fragmentation of the sprayed sample. ESI is adapted to the ionization of polar to very polar molecules, with a molecular weight ranging from around 100 to 100 000 kDa. ESI is currently the most widely used ionization technique in lipidomics. Disadvantages include the cost and a phenomenon known as ion suppression in the case of low-abundance species in complex mixtures. Absolute quantification of lipids requires class and mass independent internal standards. Miniaturized ESI, known as nanoelectrospray or nanoESI, allows the automated analysis of very large samples sets. method separating and analyzing compounds that can be vaporized without decomposition, based on their selective retention in the matrix of specific columns. GC coupled to flame ionization detection (GC-FID) allows the detection of micrograms to lower nanograms of vaporizable lipids. GC is very widely used for the determination of fatty acid profiles in glycerolipids. GC can be coupled to a mass spectrometer (GC-MS). a glycerolipid or a phospholipid, with a polar head containing a sugar. automated thin layer chromatography (TLC) system allowing the parallel analysis of a large number of samples, with higher throughput and more sensitive detection of lipids. Most recent HPTLC lines include devices that automatically couple TLC with MS (TLC-MS). database of metabolic pathways developed by the Kyoto Encyclopedia of Genes and Genomes consortium. type of biomimetic membrane made by the self-assembly of lipids in a monolayer at the air–water interface. procedure by which lipids are extracted from a mixture, based on their specific solubility in organic solvents. Usually after addition of solvents, a biphasic organic–water system is obtained and lipids are purified in the organic phase. proportions of each lipid class detected and quantified in a sample. A lipid profile is usually shown as a histogram. membrane microdomains characterized by a specific combination of glycosphingolipids, sterols and protein receptors, more ordered and tightly packed than the surrounding bilayer and involved in important biological functions. In the plasma membrane of parasites, lipid rafts are believed to be important for pathogenic processes. method separating and analyzing compounds in a liquid solution, based on their selective retention in the matrix of specific columns. High-pressure liquid chromatography (HPLC) allows the separation of lipids solubilized in organic solvents and can be coupled to a mass spectrometer (LC-MS). analytical technique that measures the mass-to-charge ratio of charged (ionized) molecules. A mass spectrometer is composed of an ion source, a mass analyzer and an ion detector. The mass analyzer can be a quadrupole (Q), a time-of-flight analyzer (TOF) or an ion trap. TOF has a very high mass accuracy. MS data are eventually represented by a spectrum composed of peaks corresponding to mass-to-charge ratios (m/z). MS peaks are specific for fragments of ionized lipid molecules. MS sensitivity allows the detection of picograms to fentograms of lipids. versatile technique used in MS to produce ions, allowing the analysis of biomolecules which tend to be fragile and fragment when ionized by other ionization methods. MALDI is often used to ionize biomolecules upstream a time-of-flight analyzer (MALDI-TOF). charged particles move in electric and magnetic fields following a path which is strictly dependent on their mass-to-charge ratio. MS peaks therefore correspond to the m/z quantities of the charged fragments hitting the detector. Neutral fragments cannot be detected. When the fragment is positively charged, this quantity is positive and vice versa. When containing only one charge, the m/z quantity corresponds to the mass of the fragment. database of metabolic pathways developed by the BioCyc consortium. a tandem MS mode used when a molecular ion, produced after fragmentation of a lipid class, loses a specific uncharged fragment. Because uncharged fragments cannot be detected, the specific loss of the corresponding neutral fragment is recorded. The lipid class can thus be characterized in a complex mixture by selecting only the initial molecular ions that lose this specific neutral fragment. Phosphatidylserine species can, for instance, be detected by constant neutral loss scans of m/z 87. a glycerolipid or a sphingolipid, which has a polar head containing a phosphate. hydrophilic moiety of polar lipids. general term defining lipids having a hydrophobic moiety and a hydrophilic polar head. Polar lipids make up the bulk of biological membranes. a tandem MS mode used when a molecular ion, produced after fragmentation of a lipid class, loses a specific charged fragment, which is then easily detected. The lipid class can thus be characterized in a complex mixture by selecting only the initial molecular ions that give this specific charged fragment. In negative ion mode, the dissociation of lipids induced in the collision chamber of a mass spectrometer can thus allow the detection of phosphatidic acid, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and phosphatidylcholine by precursor ion scans of m/z –153, –196, –241, –153 and +184. a QMS is a part of a mass spectrometer, consisting of four parallel circular rods, filtering sample ions based on their mass-to-charge ratio (m/z). Ions are thus separated based on the stability of their trajectories in the oscillating electric fields applied to the rods. Owing to the linear trajectory of ions, a QMS can be aligned in series of quadrupoles in so-called triple quadrupoles (QQQ). In a QQQ, the first QMS allows an initial analysis of ions (based on their m/z ratio) and a selection of ions of interest for subsequent fragmentation and refine analysis. The second quadrupole is then used as a collision chamber generating fragments of the ions filtered in the first QMS. The final refined MS analysis is eventually achieved in the third QMS. QQQ are tandem MS instruments that are very useful for the analysis of complex lipid mixtures. membrane microdomains in which structure and composition is similar to that of lipid rafts. also known as MS/MS, tandem MS involves multiple steps of MS selection. Between each step, a fragmentation and selection of molecular ions occurs. Tandem MS can be carried out ‘in space’ when the two MS steps are physically separated in specific instruments (triple quadrupoles or QQQ, or a quadrupole and a time-of-flight analyzer in QTOF instruments). Tandem MS can be carried out ‘in time’ in ion trap analyzers. Different modes of analyses are classically achieved with tandem MS, including the precursor ion scan and neutral loss scan modes. method of separating and analyzing molecules such as lipids on a sheet of glass, plastic or aluminum foil, coated with a thin layer of absorbent material, usually silica gel. Typically inexpensive and very well established, this technique has a low resolution in direct semiquantification using lipid specific dyes; however, it allows the detection of low micrograms of lipids when coupled to GC, and in most recent techniques, it is efficient in the picogram range, when automatically coupled to MS. a TOF is part of a mass spectrometer, in which the mass-to-charge ratio (m/z) of ions is determined after their acceleration by an electric field of known strength and record of the time it takes the ion to reach a detector. TOF MS has a very high mass accuracy. A QTOF is a tandem MS instrument in which an initial quadrupole filters sample ions based on their mass-to-charge ratio (m/z). After fragmentation, the filtered ions are then separated in a TOF analyzer." @default.
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• W1980355616 date "2011-11-01" @default.
• W1980355616 modified "2023-10-17" @default.
• W1980355616 title "Membrane lipidomics for the discovery of new antiparasitic drug targets" @default.
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• W1980355616 doi "https://doi.org/10.1016/j.pt.2011.07.002" @default.
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