1429-59-0Relevant academic research and scientific papers
Development of isotope-enriched phosphatidylinositol-4- And 5-phosphate cellular mass spectrometry probes
Joffrin, Amélie M.,Saunders, Alex M.,Barneda, David,Flemington, Vikki,Thompson, Amber L.,Sanganee, Hitesh J.,Conway, Stuart J.
, p. 2549 - 2557 (2021/03/01)
Synthetic phosphatidylinositol phosphate (PtdInsPn) derivatives play a pivotal role in broadening our understanding of PtdInsPnmetabolism. However, the development of such tools is reliant on efficient enantioselective and regioselective synthetic strategies. Here we report the development of a divergent synthetic route applicable to the synthesis of deuterated PtdIns4Pand PtdIns5Pderivatives. The synthetic strategy developed involves a key enzymatic desymmetrisation step using Lipozyme TL-IM. In addition, we optimised the large-scale synthesis of deuteratedmyo-inositol, allowing for the preparation of a series of saturated and unsaturated deuterated PtdIns4Pand PtdIns5Pderivatives. Experiments in MCF7 cells demonstrated that these deuterated probes enable quantification of the corresponding endogenous phospholipids in a cellular setting. Overall, these deuterated probes will be powerful tools to help improve our understanding of the role played by PtdInsPnin physiology and disease.
Synthesis and enantiospecific analysis of enantiostructured triacylglycerols containing n-3 polyunsaturated fatty acids
Gudmundsson, Haraldur G.,Haraldsson, Gudmundur G.,Kallio, Heikki,Kalpio, Marika,Linderborg, Kaisa M.,Magnússon, Jóhann D.,Yang, Baoru
, (2020/07/08)
The stereospecific structure of triacylglycerols (TAGs) affects the bioavailability of fatty acids. Lack of enantiopure reference compounds and effective enantiospecific methods have hindered the stereospecific analysis of individual TAGs. Twelve novel enantiostructured AAB-type TAGs were synthesized containing one of the three n-3 polyunsaturated fatty acid: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) in sn-1 or sn-3 position. These compounds formed six enantiomer pairs, which were separated with recycling high-performance liquid chromatography using chiral columns and UV detection. The chromatographic retention behavior of the enantiomers and the stereospecific elution order were studied. The enantiomer with an n-3 PUFA in the sn-1 position eluted faster than the enantiomer with the n-3 PUFA in the sn-3 position, regardless of the carbon chain length and number of double bonds of the PUFA. TAG enantiomers containing DHA exhibited highly different retention on the chiral column and were separated after the first column, whereas recycling was needed to separate the enantiomer pairs containing ALA or EPA. The system using two identical columns and one mobile phase, without sample derivatization, proved to be very effective also for peak purity assessment, confirming the enantiopurity of the synthesized structured TAGs being higher than 98 percent (96 percent ee).
Preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant S
Manzo, Emiliano,Fioretto, Laura,Gallo, Carmela,Ziaco, Marcello,Nuzzo, Genoveffa,D’Ippolito, Giuliana,Borzacchiello, Assunta,Fabozzi, Antonio,de Palma, Raffaele,Fontana, Angelo
, (2020/10/02)
In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential.
Stereochemical Analysis of Glycerophospholipids by Vibrational Circular Dichroism
Taniguchi, Tohru,Manai, Daisuke,Shibata, Masataka,Itabashi, Yutaka,Monde, Kenji
, p. 12191 - 12194 (2015/10/12)
The stereochemistry of glycerophospholipids (GPLs) has been of interest for its roles in the evolution of life and in their biological activity. However, because of their structural complexity, no convenient method to determine their configuration has been reported. In this work, through the first systematic application of vibrational circular dichroism (VCD) spectroscopy to various diacylated GPLs, we have revealed that their chirality can be assigned by the sign of a VCD exciton couplet generated by the interaction of two carbonyl groups. This paper also presents spectroscopic evidence for the stereochemistry of GPLs isolated from bacteria, eukaryotes, and mitochondria.
Synthesis of unsaturated phosphatidylinositol 4-phosphates and the effects of substrate unsaturation on SopB phosphatase activity
Furse, Samuel,Mak, Lokhang,Tate, Edward W.,Templer, Richard H.,Ces, Oscar,Woscholski, Rüdiger,Gaffney, Piers R. J.
supporting information, p. 2001 - 2011 (2015/03/05)
In this paper evidence is presented that the fatty acid component of an inositide substrate affects the kinetic parameters of the lipid phosphatase Salmonella Outer Protein B (SopB). A succinct route was used to prepare the naturally occurring enantiomer of phosphatidylinositol 4-phosphate (PI-4-P) with saturated, as well as singly, triply and quadruply unsaturated, fatty acid esters, in four stages: (1) The enantiomers of 2,3:5,6-O-dicyclohexylidene-myo-inositol were resolved by crystallisation of their di(acetylmandelate) diastereoisomers. (2) The resulting diol was phosphorylated regio-selectively exclusively on the 1-O using the new reagent tri(2-cyanoethyl)phosphite. (3) With the 4-OH still unprotected, the glyceride was coupled using phosphate tri-ester methodology. (4) A final phosphorylation of the 4-O, followed by global deprotection under basic then acidic conditions, provided PI-4-P bearing a range of sn-1-stearoyl, sn-2-stearoyl, -oleoyl, -γ-linolenoyl and arachidonoyl, glycerides. Enzymological studies showed that the introduction of cis-unsaturated bonds has a measurable influence on the activity (relative Vmax) of SopB. Mono-unsaturated PI-4-P exhibited a five-fold higher activity, with a two-fold higher KM, over the saturated substrate, when presented in DOPC vesicles. Poly-unsaturated PI-4-P showed little further change with respect to the singly unsaturated species. This result, coupled with our previous report that saturated PI-4-P has much higher stored curvature elastic stress than PI, supports the hypothesis that the activity of inositide phosphatase SopB has a physical role in vivo. This journal is
Synthesis of enantiopure structured triacylglycerols
Kristinsson, Bjoern,Linderborg, Kaisa M.,Kallio, Heikki,Haraldsson, Gudmundur G.
, p. 125 - 132 (2014/02/14)
The synthesis of nine enantiopure structured triacylglycerols (TAGs) of the AAB type is described, all possessing the (S)-absolute configuration. Six of them possess one saturated and two identical unsaturated fatty acyl chains, whereas the remaining three possess two identical saturated fatty acids along with one unsaturated fatty acid. The former group was synthesized by a five-step chemoenzymatic route involving a highly regioselective immobilized Candida antarctica lipase, starting from enantiopure (R)-solketal. The second group was prepared by a fully chemical five-step approach based on the same chiral precursor. Such enantiopure TAGs are strongly required as standards for the enantiospecific analysis of intact TAGs in fats and oils.
PHOSPHATIDYLINOSITOL
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Page/Page column 20; 21, (2013/06/27)
The invention relates to a new pharmaceutical compound, diacyl phosphatdylinositol in which both the sn-1 and the sn-2 place are taken by stearic acid (18:0) (diacyl [18:0; 18:0] phosphatidylinositol), more preferably, wherein said diacyl phosphatidylinositol is compound 1 as depicted in Fig. 10 or a racemate of compounds 1 and 2 as depicted in Fig. 10. Said pharmaceutical compound and pharmaceutical compositions comprising this compound are specifically useful for the treatment of a disease or a condition wherein suppression of T-cell activation is desirable, such as asthma, diabetes Type 1, rheumatoid arthritis, inflammatory bowel disease or psoriasis. Also part of the invention are food items containing the compound(s) of the invention and use thereof in a diet to treat or prevent the disease or condition mentioned above
Synthesis of novel, fluorescently tagged analogs of glycosylphosphatidylinositol (GPI) anchors
Johnson, Charles L.,Guo, Zhongwu
, p. 301 - 323 (2013/10/08)
Glycosylphosphatidylinositol (GPI) anchors are a group of complex glycolipids that attach extracellular proteins and glycoproteins to the eukaryotic cell outer membrane. To better understand GPI anchorage, it is necessary to have access to homogeneous, structurally defined, and functionalized GPIs and GPI analogs. In this regard, chemical synthesis is necessary, as GPI anchors are rather scarce and heterogeneous in natural sources. Three GPI analogs with phosphoglycerolipids linked to the pseudodisaccharide core and their fluorescein conjugates were prepared in this work as a small tool set useful for probing how the lipid composition and carbohydrate anomeric configuration may affect the properties of GPI anchors.
Synthesis of boron cluster lipids: Closo-dodecaborate as an alternative hydrophilic function of boronated liposomes for neutron capture therapy
Lee, Jong-Dae,Ueno, Manabu,Miyajima, Yusuke,Nakamura, Hiroyuki
, p. 323 - 326 (2008/02/03)
(Chemical Equation Presented) We succeeded in the synthesis of the double-tailed boron cluster lipids 4a-c and 5a-c, which have a B 12H11S moiety as a hydrophilic function, by S-alkylation of B12H11SH (BSH) with bromoacetyl and chloroacetocarbamate derivatives of diacylglycerols for a liposomal boron delivery system on neutron capture therapy. Calcein encapsulation experiments revealed that the liposomes, prepared from the boron cluster lipid 4b, DMPC, PEG-DSPE, and cholesterol, are stable at 37°C in FBS solution for 24 h.
Phosphorylation of unnatural phosphatidylinositols with phosphatidylinositol 3-kinase
Morisaki, Naoko,Morita, Koji,Nishikawa, Asuka,Nakatsu, Noriyuki,Fukui, Yasuhisa,Hashimoto, Yuichi,Shirai, Ryuichi
, p. 2603 - 2614 (2007/10/03)
Phosphatidylinositol analogs (PI(C2)-PI(C18)) having a series of saturated fatty acid (C2-C18) at sn-2 position were synthesized and subjected to the phosphorylation reaction with phosphatidylinositol 3-kinase (PI 3- kinase). The reactivity of Pica with PI 3-kinase turned out to be comparable to that of natural PI, although PI(C18) was not phosphorylated under the same condition. The chirality of sn-2 center was not responsible for the phosphorylation reaction. (C) 2000 Elsevier Science Ltd.
