10022-13-6Relevant articles and documents
A facile and stereoselective synthesis of 3,4,6-tri-O-acetyl-2-deoxy-2- phthalimido-β-D-glucopyranosyl chloride
Cao, Zhiling,Liu, Wenjie,Qu, Yingying,Yao, Guowei,Gao, Dachao,Liu, Weiwei
, p. 467 - 469 (2013)
Acetylation of D-glucosamine catalysed by sulfuric acid and N-phthaloylation of the glucosyl acetate yielded 1,3,4,6- tetra-O-acetyl-2- deoxy-2-phthalimido-α-D-glucopyranose. This gave the corresponding pure β-glucosyl chloride upon treatment with PCl5-BF3. An anomeric chlorination with thionyl chloride combined with the Lewis acids (ZnCl2, SnCl4 and BiCl3) resulted in an α/β anomer mixture.
Enhanced binding to DNA and topoisomerase I inhibition by an analog of the antitumor antibiotic rebeccamycin containing an amino sugar residue
Bailly, Christian,Qu, Xiaogang,Anizon, Fabrice,Prudhomme, Michelle,Riou, Jean-Francois,Chaires, Jonathan B.
, p. 377 - 385 (1999)
Many antitumor agents contain a carbohydrate side chain appended to a DNA-intercalating chromophore. This is the case with anthracyclines such as daunomycin and also with indolocarbazoles including the antibiotic rebeccamycin and its tumor active analog, NB506. In each case, the glycoside residue plays a significant role in the interaction of the drug with the DNA double helix. In this study we show that the DNA-binding affinity and sequence selectivity of a rebeccamycin derivative can be enhanced by replacing the glucose residue with a 2'-aminoglucose moiety. The drug-DNA interactions were studied by thermal denaturation, fluorescence, and footprinting experiments The thermodynamic parameters indicate that the newly introduced amino group on the glycoside residue significantly enhanced binding to DNA by increasing the contribution of the polyelectrolyte effect to the binding free energy, but does not appear to participate in any specific molecular contacts. The energetic contribution of the amino group of the rebeccamycin analog was found to be weaker than that of the sugar amino group of daunomycin, possibly because the indolocarbazole derivative is only partially charged at neutral pH. Topoisomerase I-mediated DNA cleavage studies reveal that the OH→NH2 substitution does not affect the capacity of the drug to stabilize enzyme-DNA covalent complexes. Cytotoxicity studies with P388 leukemia cells sensitive or resistant to camptothecin suggest that topoisomerase I represents a privileged intracellular target for the studied compounds. The role of the sugar amino group is discussed. The study provides useful guidelines for the development of a new generation of indolocarbazole- based antitumor agents.
Direct and efficient monitoring of glycosyltransferase reactions on gold colloidal nanoparticles by using mass spectrometry
Nagahori, Noriko,Nishimura, Shin-Ichiro
, p. 6478 - 6485 (2006)
A simple and efficient assay for glycosyltransferase activity on gold colloidal nanoparticles (GCNPs) by using laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS) is demonstrated by the enzymatic synthesis of the Lewis X trisaccharide on GCNPs containing GlcNAc residues. GCNPs containing multivalent sugars were well dispersed in aqueous solution and proved to be excellent acceptor substrates for the glycosyltransferase reaction. Direct LDI-TOF MS analysis of these GCNPs provided the ion peaks of the sugar derivatives, chemisorbed through S-Au linkages onto the GCNPs, even in the presence of contaminants such as proteins and salts. Thus, it enabled the rapid and direct detection of the enzymatic reaction on the GCNPs by subjecting a small amount (0.15 μL) of the reaction mixture to MS analysis without purification. Subsequent MS/MS analyses (LDI-LIFT-TOF/TOF method) of the product-carrying GCNPs enabled the structures of the sugar derivatives that had been constructed on the GCNPs by enzymatic glycosylation to be determined. A quantitative inhibition assay for glycosyltransferase by using LDI-TOF MS analysis on the GCNPs was demonstrated by using uridine 5′-di-phosphate (UDP) as the inhibitor. This simple assay was then applied to the detection of the enzymatic activity of a crude cell extract of Escherichia coli, which produces Neisseria meningitidis β-1,4-galactosyltransferase (β-1,4-GalT). In this case, the GCNPs were roughly purified by means of ultrafiltration to remove the buffer and detergents before MS analysis. That the GCNPs are dissolved in solution in the reaction medium but are solid in the purification process is greatly advantageous for the simple and efficient detection of enzymatic activity in crude biological samples. Thus, GCNPs containing a variety of biomolecules may become a versatile and efficient tool for the rapid and direct monitoring of metabolism (metabolomics) in living cells when combined with LDI-TOF MS analysis.
A practical synthesis of a (1→6)-linked β-D-glucosamine nonasaccharide
Yang, Feng,Du, Yuguo
, p. 495 - 502 (2003)
A (1→6)-β-D-glucosamine nonasaccharide was convergently synthesized using isopropyl thioglycosides as donors. Anomeric acetylated glucosamine derivatives were proved to be good acceptors in the NIS/TMSOTf catalyzed glycosylation. The target nonasaccharide showed a mild antitumor activity against H22 on the preliminary mice tests.
Synthesis and immunological evaluation of a low molecular weight saccharide with TLR-4 agonist activity
Basava, Vikram,Romlein, Heather,Bitsaktsis, Constantine,Marzabadi, Cecilia H.
, p. 697 - 705 (2017)
The paucity of FDA approved adjuvants renders the synthesis, characterization, and use of new compounds as vaccine adjuvants, a necessity. For this purpose, a novel saccharide analog has been synthesized from glucosamine, pyruvylated galactose and 1,4-cyclohexanediol and its biological efficacy was determined in innate immune cells. More specifically, we assessed the production of pro-inflammatory cytokines from the murine monocyte cell line, Raw 264.7 and from C57 BL/6 mouse peritoneal macrophages following exposure to the saccharide analog. Our data conclude that the novel saccharide has immunostimulatory activity on mouse macrophages as indicated by the elevated levels of IL-6 and TNF-α in culture supernatants. This effect was TLR-4-dependent but TLR-2-independent. Our data, suggest TLR-4 agonism; a key feature of vaccine adjuvants.
Improved synthesis of 1,2-trans-acetates and 1,2-trans ethyl 1-thioglycosides derived from 3,4,6-tri-o-acetyl-2-deoxy-2-phthalimido-D-hexopyranosides
Vesely, Jan,Ledvina, Miroslav,Jindrich, Jindrich,Saman, David,Trnka, Tomas
, p. 1264 - 1274 (2003)
Effective one-pot synthesis of 1,2-trans-acetates 4b, 5b and 6a derived from N-phthaloyl-protected D-glucosamine, D-galactosamine and D-mannosamine, respectively, is presented. Anomerisation of the corresponding 1,2-cis-acetates 4a, 5a and 6b and direct conversion of all of them to 1,2-trans ethyl 1-thioglycosides 7, 8 and 9 are also described and discussed.
Selectively Deoxyfluorinated N-Acetyllactosamine Analogues as 19F NMR Probes to Study Carbohydrate-Galectin Interactions
Kurfi?t, Martin,Dra?ínsky, Martin,?ervenková ??astná, Lucie,Cu?ínová, Petra,Hamala, Vojtěch,Hovorková, Michaela,Bojarová, Pavla,Karban, Jind?ich
supporting information, p. 13040 - 13051 (2021/08/07)
Galectins are widely expressed galactose-binding lectins implied, for example, in immune regulation, metastatic spreading, and pathogen recognition. N-Acetyllactosamine (Galβ1-4GlcNAc, LacNAc) and its oligomeric or glycosylated forms are natural ligands of galectins. To probe substrate specificity and binding mode of galectins, we synthesized a complete series of six mono-deoxyfluorinated analogues of LacNAc, in which each hydroxyl has been selectively replaced by fluorine while the anomeric position has been protected as methyl β-glycoside. Initial evaluation of their binding to human galectin-1 and -3 by ELISA and 19F NMR T2-filter revealed that deoxyfluorination at C3, C4′ and C6′ completely abolished binding to galectin-1 but very weak binding to galectin-3 was still detectable. Moreover, deoxyfluorination of C2′ caused an approximately 8-fold increase in the binding affinity towards galectin-1, whereas binding to galectin-3 was essentially not affected. Lipophilicity measurement revealed that deoxyfluorination at the Gal moiety affects log P very differently compared to deoxyfluorination at the GlcNAc moiety.
Reduction Triggered in Situ Polymerization in Living Mice
Chen, Zixin,Cui, Lina,Fréchet, Jean M. J.,Gambhir, Sanjiv S.,Kierstead, Paul H.,Kothapalli, Sri-Rajasekhar,Liu, Jun,Ma, Xiaowei,Rao, Jianghong,Smith, Bryan Ronain,Taylor, Madelynn,Vivona, Sandro
supporting information, p. 15575 - 15584 (2020/10/18)
"Smart"biomaterials that are responsive to physiological or biochemical stimuli have found many biomedical applications for tissue engineering, therapeutics, and molecular imaging. In this work, we describe in situ polymerization of activatable biorthogonal small molecules in response to a reducing environment change in vivo. We designed a carbohydrate linker- and cyanobenzothiazole-cysteine condensation reaction-based small molecule scaffold that can undergo rapid condensation reaction upon physiochemical changes (such as a reducing environment) to form polymers (pseudopolysaccharide). The fluorescent and photoacoustic properties of a fluorophore-tagged condensation scaffold before and after the transformation have been examined with a dual-modality optical imaging method. These results confirmed the in situ polymerization of this probe after both local and systemic administration in living mice.
