- Engineering the Mycomembrane of Live Mycobacteria with an Expanded Set of Trehalose Monomycolate Analogues
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Mycobacteria and related organisms in the Corynebacterineae suborder are characterized by a distinctive outer membrane referred to as the mycomembrane. Biosynthesis of the mycomembrane occurs through an essential process called mycoloylation, which involv
- Fiolek, Taylor J.,Banahene, Nicholas,Kavunja, Herbert W.,Holmes, Nathan J.,Rylski, Adrian K.,Pohane, Amol Arunrao,Siegrist, M. Sloan,Swarts, Benjamin M.
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- Synthesis of 6,6′-Bis(O-4-arylethynylbenzoyl)-α,α-Trehaloses and Their Utilization as Fluorescent Probes for Cellular Imaging
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A series of 6,6′-bis(O-4-arylethynylbenzoyl)-α,α-trehaloses (aryl groups; 1a: 1-pyrenyl, 1b: 9-anthryl, 1c: phenyl) were synthesized and fully characterized. Their photophysical properties were investigated by UV/Vis/fluorescence spectroscopy, and were rationalized by TDDFT calculations. Moreover, the emission maxima of 1a and 1b in THF/H2O considerably shifted to a longer wavelength region with increasing H2O fraction owing to the formation of excimers. The pyrenyl derivative 1a was efficiently taken into HeLa CD4+ human cervical cancer cells and emitted bright green fluorescence.
- Kobayashi, Kurumi,Saito, Rumiko,Udagawa, Kaori,Miyano-Kurosaki, Naoko,Asano, Naoto,Iwanaga, Tetsuo,Teramoto, Naozumi,Shimasaki, Toshiaki,Shibata, Mitsuhiro
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- Synthesis of maradolipid
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The first synthesis of maradolipid, a unique dissymmetrically 6,6′-di-O-acylated trehalose glycolipid isolated from C. elegans, is accomplished in five steps starting from trehalose in 45% overall yield. The short synthesis relies on dissymmetrization of trehalose core via regioselective acylation of a 2,3,4,2′,3′,4′-hexa-O-TMS trehalose 6,6′-diol derivative as a key step.
- Sarpe, Vikram A.,Kulkarni, Suvarn S.
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- Trehalose-based neuroprotective autophagy inducers
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A small set of trehalose-centered putative autophagy inducers was rationally designed and synthesized, with the aim to identify more potent and bioavailable autophagy inducers than free trehalose, and to acquire information about their molecular mechanism
- Arosio, Daniela,Assoni, Giulia,Colombo, Eleonora,Frapporti, Giulia,Gornati, Davide,Perez-Carrion, Maria Dolores,Piccoli, Giovanni,Polito, Laura,Seneci, Pierfausto
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supporting information
(2021/03/23)
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- Nanolipid-trehalose conjugates and nano-assemblies as putative autophagy inducers
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The disaccharide trehalose is an autophagy inducer, but its pharmacological application is severely limited by its poor pharmacokinetics properties. Thus, trehalose was coupled via suitable spacers with squalene (in 1:2 and 1:1 stoichiometry) and with betulinic acid (1:2 stoichiometry), in order to yield the corresponding nanolipid-trehalose conjugates 1-Sq-mono, 2-Sq-bis and 3-Be-mono. The conjugates were assembled to produce the corresponding nano-assemblies (NAs) Sq-NA1, Sq-NA2 and Be-NA3. The synthetic and assembly protocols are described in detail. The resulting NAs were characterized in terms of loading and structure, and tested in vitro for their capability to induce autophagy. Our results are presented and thoroughly commented upon.
- Colombo, Eleonora,Biocotino, Michele,Frapporti, Giulia,Randazzo, Pietro,Christodoulou, Michael S.,Piccoli, Giovanni,Polito, Laura,Seneci, Pierfausto,Passarella, Daniele
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- Lipid length and iso-branching of trehalose diesters influences Mincle agonist activity
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We report on the efficient synthesis of linear trehalose diesters (TDEs) and iso-branched TDEs (maradolipids or iso-TDEs) and their ability to activate bone marrow-derived macrophages (BMDMs) as determined by cytokine (IL-1β IL-12, IL-6, IL-10) and chemokine (MIP-2) production. Both classes of TDEs were found to activate BMDMs in a Mincle-dependent manner, with longer-chain (≥C18) lipids leading to a robust inflammatory response. On the whole, the iso-branched TDEs led to greater cytokine production and a faster immune response when compared to their linear counterparts. Moreover, C12-TDE and iso-C12-TDE elicited the production of MIP-2 by BMDMs, thereby providing the first example of TDEs with a chain length of ≤ C12 leading to a Mincle-dependent immune response and one that is less inflammatory in nature.
- Khan, Ayesha,Kodar, Kristel,Timmer, Mattie S.M.,Stocker, Bridget L.
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p. 1269 - 1277
(2017/12/11)
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- BIODEGRADABLE TREHALOSE GLYCOPOLYMERS
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Structures and methods of making biodegradable trehalose co-polymers are disclosed. Specifically, biodegradable trehalose co-polymers consist of the general structure R5-[R1R2C - CR3R4]n-[DG]m/s
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Paragraph 00220-00221
(2016/02/29)
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- Synthesis of a mycobacterium tuberculosis tetra-acylated sulfolipid analogue and characterization of the chiral acyl chains using anisotropic NAD 2D-NMR spectroscopy
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Tetra-O-acylated sulfolipids are metabolites found in the cell wall of Mycobacterium tuberculosis, the causative agent of tuberculosis. Their role in pathogenesis remains, however, undefined. Here we describe a novel access to model tetra-O-acylated treha
- Lemetais, Aurelie,Bourdreux, Yann,Lesot, Philippe,Farjon, Jonathan,Beau, Jean-Marie
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p. 7648 - 7657
(2013/09/02)
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- Synthesis and structure - Activity relationships studies of brartemicin analogs as anti-invasive agents
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Brartemicin is a trehalose-based inhibitor of tumor cell invasion produced by the actinomycete of the genus Nonomuraea. In order to find more potent anti-invasive agents and study the structure-activity relationships, a series of 19 brartemicin analogs we
- Jiang, Yong-Li,Miyanaga, Satoshi,Han, Xiu-Zhen,Tang, Long-Qiang,Igarashi, Yasuhiro,Saiki, Ikuo,Liu, Zhao-Peng
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p. 531 - 537
(2013/10/21)
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- Simple one-pot regioselective 6-O-phosphorylation of carbohydrates and trehalose desymmetrization
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Biologically essential carbohydrate 6-phosphates, especially trehalose 6-phosphate, can be synthesized easily in excellent overall yields in 2 steps involving minimum protecting group manipulations. We can cleave the diphenylphosphate group for further synthetic objectives.
- Abragam Joseph,Chang, Chun-Wei,Wang, Cheng-Chung
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supporting information
p. 11497 - 11499
(2013/12/04)
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- TMSOTf-catalyzed silylation: Streamlined regioselective one-pot protection and acetylation of carbohydrates
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A highly efficient TMSOTf-catalyzed HMDS silylation of sugars, which can easily be integrated with subsequent reactions in one-pot fashion, has been developed. Its usefulness was demonstrated by applications to streamlined regioselective one-pot protection and nonenzymatic acetylation of unprotected sugars. Monosaccharide and trehalose building blocks with orthogonally well-differentiated hydroxy groups were efficiently prepared starting with free sugars in one-pot fashion without the need for prior per-O-silylation. Regioselectively protected and acetylated building blocks were prepared directly from unprotected sugars in a one-pot manner involving up to five TMSOTf-catalyzed reactions, including a new TMSOTf-catalyzed silylation of carbohydrates. Copyright
- Joseph, A. Abragam,Verma, Ved Prakash,Liu, Xin-Yi,Wu, Chia-Hui,Dhurandhare, Vijay M.,Wang, Cheng-Chung
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experimental part
p. 744 - 753
(2012/03/11)
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- Iron(iii) chloride-tandem catalysis for a one-pot regioselective protection of glycopyranosides
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Tandem catalysis by using iron(iii) chloride hexahydrate leads to carbohydrate building blocks displaying an orthogonal protecting group pattern as illustrated by the regioselective protection of trehalose and maltose disaccharides.
- Bourdreux, Yann,Lemetais, Aurelie,Urban, Dominique,Beau, Jean-Marie
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supporting information; experimental part
p. 2146 - 2148
(2011/04/21)
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- Synthesis of ten members of the maradolipid family; Novel diacyltrehalose glycolipids from caenorhabditis elegans
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The synthesis of ten members of the maradolipid family is described using a direct route starting from trehalose. Georg Thieme Verlag Stuttgart · New York.
- P?ssler, Ulrike,Gruner, Margit,Penkov, Sider,Kurzchalia, Teymuras V.,Kn?lker, Hans-Joachim
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scheme or table
p. 2482 - 2486
(2011/11/12)
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- Time-dependent profiling of metabolites from Snf1 mutant and wild type yeast cells
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The effect of sampling time in the context of growth conditions on a dynamic metabolic system was investigated in order to assess to what extent a single sampling time may be sufficient for general application, as well as to determine if useful kinetic information could be obtained. A wild type yeast strain (W) was compared to a snf1Δ mutant yeast strain (S) grown in high-glucose medium (R) and in low-glucose medium containing ethanol (DR). Under these growth conditions, different metabolic pathways for utilizing the different carbon sources are expected to be active. Thus, changes in metabolite levels relating to the carbon source in the growth medium were anticipated. Furthermore, the Snf1 protein kinase complex is required to adapt cellular metabolism from fermentative R conditions to oxidative DR conditions. So, differences in intracellular metabolite levels between the W and S yeast strains were also anticipated. Cell extracts were collected at four time points (0.5, 2, 4, 6 h) after shifting half of the cells from R to DR conditions, resulting in 16 sample classes (WR, WDR, SR, SDR) x (0.5, 2, 4, 6 h). The experimental design provided time course data, so temporal dependencies could be monitored in addition to carbon source and strain dependencies. Comprehensive two-dimensional (2D) gas chromatography coupled to time-of-flight mass spectrometry (GC x GC-TOFMS) was used with discovery-based data mining algorithms (Anal. Chem. 2006, 78, 5068-5075 (ref 1); J. Chromatogr., A 2008, 1186, 401-411 (ref 2)) to locate regions within the 2D chromatograms (i.e., metabolites) that provided chemical selectivity between the 16 sample classes. These regions were mathematically resolved using parallel factor analysis to positively identify the metabolites and to acquire quantitative results. With these tools, 51 unique metabolites were identified and quantified. Various time course patterns emerged from these data, and principal component analysis (PCA) was utilized as a comparison tool to determine the sources of variance between these 51 metabolites. The effect of sampling time was investigated with separate PCA analyses using various subsets of the data. PCA utilizing all of the time course data, averaged time course data, and each individual time point data set independently were performed to discern the differences. For the yeast strains examined in the current study, data collection at either 4 or 6 h provided information comparable to averaged time course data, albeit with a few metabolites missing using a single sampling time point.
- Humston, Elizabeth M.,Dombek, Kenneth M.,Hoggard, Jamin C.,Young, Elton T.,Synovec, Robert E.
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experimental part
p. 8002 - 8011
(2009/04/06)
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- Synthesis of glycosyl strapped porphyrins
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In this paper, we present the synthesis of two glycosylated strapped porphyrins. Structural elucidation is described (1H NMR, MS Maldi and UV visible). The photocytotoxicity of these glycosyl strapped porphyrins against carcinogenic K562 cells
- Davoust,Granet,Krausz,Carre,Guilloton
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p. 2513 - 2516
(2007/10/03)
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- Gram-scale synthesis of α,α-trehalose 6-monophosphate and α,α- trehalose 6,6'-diphosphate
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α,α-Trehalose derivatives α,α-trehalose 6-monophosphate and α,α-trehalose 6,6′-diphosphate were synthesized to investigate their biological properties of the nonreducing disaccharide. These compounds were significant to the biosynthetic pathway since α,α-trehalose 6-phosphate serves as an intermediate of α,α-trehalose. α,α-Trehalose 6-phosphate was also found to be significant in regulating the first steps of yeast glycolysis. In this paper, a number of methods was described to derive the α,α-trehalose phosphates. Trimethylsilylation and selective methanolysis of primary trimethylsilyloxy group were used.
- Ronnow,Meldal,Bock
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p. 323 - 328
(2007/10/02)
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- An improved synthesis of trehalose 6-mono- and 6,6'-di-corynomycolates and related esters
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A simplified synthesis of 6-mono- and 6,6'-di-corynomycolate esters of α,α-trehalose, and related compounds, was achieved by coupling the (hydroxyl-protected) acids to the partially trimethylsilylated sugar in the presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine.As acid reactants, (2-RS,3-RS)-3-hydroxy-2-tetradecyloctadecanoic acid (DL-corynomycolic acid) and its 2RS, 3SR diastereomer were prepared from methyl palmitate by sequential Claisen condensation, reduction, chromatographic separation, and saponification.Reaction with tert-butylchlorodimethylsilane (imidazole) gave the disubstituted ether-esters, which were converted into the required 3-tert-butyldimethylsilyl ethers by partial hydrolysis. 6-Linked monocorynomycolate was obtained in excellent yield (78percent) from the reaction of the RS,SR acid with the known heptakis-O-(trimethylsilyl)trehalose, and in good yield from equimolar portions of RS,RS acid and hexakis-O-(trimethylsilyl)trehalose.An excess (2.5-molar portions) of the RS,RS acid gave the 6,6'-diester (69percent).The mono- and di-palmitate were similarly obtained from (Me3Si)6-trehalose.The mono (RS,RS)-(Me3Si)6-trehalose coupling product was partially resolved on a silica gel column into its RR and SS diastereomers, the former corresponding to the naturally occurring trehalose monocorynomycolate.All coupling products were deprotected to free trehalose esters by treatment first with K2CO3 in methanol, then tetrabutylammonium fluoride-trifluoracetic acid in oxolane.
- Datta, Arun K.,Takayama, Kuni,Nashed, Mina A.,Anderson, Laurens
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