51450-09-0Relevant articles and documents
Synthesis of Novel Dendritic Glycosides
Zanini, Diana,Park, William K. C.,Roy, Rene
, p. 7383 - 7386 (1995)
Dendritic thiolated glycosides, with and without a spacer moiety, exhibiting valencies of two, four and eight were synthesized using L-lysine as a divalent core structure via solid-phase chemistry.
Magnetic nanoparticles-templated assembly of protein subunits: A new platform for carbohydrate-based MRI nanoprobes
Valero, Elsa,Tambalo, Stefano,Marzola, Pasquina,Ortega-Munoz, Mariano,Lopez-Jaramillo, F. Javier,Santoyo-Gonzalez, Francisco,De Dios Lopez, Juan,Delgado, Juan J.,Calvino, Jose J.,Cuesta, Rafael,Dominguez-Vera, Jose M.,Galvez, Natividad
, p. 4889 - 4895 (2011)
A new approach for the preparation of carbohydrate-coated magnetic nanoparticles is reported. In a first step, we show that the pH-driven assembly-disassembly natural process that occurs in apoferritin protein is effective for the encapsulation of maghemite nanoparticles of different sizes: 4 and 6 nm. In a second step, we demonstrate that the presence of functional amine groups in the outer shell of apoferritin allows functionalization with two carbohydrates, N-acetyl-d-glucosamine and d-mannose. High-resolution electron microscopy (HREM), high angle annular dark field scanning electron microscopy (HAADF-STEM), electron energy loss spectroscopy (EELS), X-ray diffraction (XRD), and SQUID technique have been used to characterize the magnetic samples, termed herein Apomaghemites. The in vivo magnetic resonance imaging (MRI) studies showed the efficiency in contrasting images for these samples; that is, the r2 NMR relaxivities are comparable with Endorem (a commercial superparamagnetic MRI contrast agent). The r2 relaxivity values as well as the pre-contrast and post-contrast T2*-weighted images suggested that our systems could be used as perspective superparamagnetic contrast agents for magnetic resonance imaging (MRI). The carbohydrate- functionalized Apomaghemite nanoparticles retained their recognition abilities, as demonstrated by the strong affinity with their corresponding carbohydrate-binding lectins.
Glycoclusters as lectin inhibitors: Comparative analysis on two plant agglutinins with different folding as a step towards rules for selectivity
André, Sabine,O'Sullivan, Shane,Gabius, Hans-Joachim,Murphy, Paul V.
, p. 6867 - 6880 (2015)
The emerging physiological significance of carbohydrate (glycan)-protein (lectin) recognition engenders the interest to design synthetic inhibitors with a high level of selectivity among natural sugar receptors. Plant agglutinins are common models to dete
Improved Synthesis of 1-Glycosyl Thioacetates and Its Application in the Synthesis of Thioglucoside Gliflozin Analogues
Dong, Hai,Feng, Guang-Jing,Luo, tao,Lv, Jian,Wang, Shuang-Shuang,Wu, Yuzhou
, p. 2940 - 2949 (2021/07/26)
An improved method to synthesize 1-glycosyl thioacetates was developed, where per-O-acetylated glycoses were allowed to directly react with potassium thioacetate (KSAc) in the presence of BF3 ? Et2O in ethyl acetate under mild conditions. This method not only overcomes the disadvantage of the traditional one-step method, which is that the odorous and toxic thioacetic acid has to be used, but also overcomes the disadvantage of the traditional two-step method, which is that the unstable intermediate, glycosyl halide, has to be synthesized from the per-O-acetylated glycose in advance. Based on this, the per-O-acetylated glucosyl disulfide and the per-O-acetylated glucosyl 1-thiol were efficiently synthesized in high yields (91 % and 90 % respectively) starting from per-O-acetylated glycoses in two-step without the need to isolate intermediate products. Through metal-catalyzed cross-coupling of per-O-acetylated glucosyl 1-thiol with aryl-iodide under very mild conditions, two thioglucoside gliflozin analogues were efficiently synthesized in high yields for the first time. These two thioglucoside gliflozin analogues were further confirmed to be stable to hydrolysis of β-glucosidase.
GOLD COMPOSITIONS AND METHODS OF USE THEREOF
-
Paragraph 0064; 0071; 0078, (2020/03/05)
Gold compounds and pharmaceutically acceptable salts thereof are disclosed. Certain compounds and salts are active as antibacterial, antifungal, and/or anti-parasitic agents. The disclosure provides pharmaceutical compositions containing the gold compounds. Methods of using the gold compounds to treat bacterial infections are disclosed.
Synthesis and Structure-Activity Relationship Study of Antimicrobial Auranofin against ESKAPE Pathogens
Wu, Bin,Yang, Xiaojian,Yan, Mingdi
, p. 7751 - 7768 (2019/09/10)
Auranofin, an FDA-approved arthritis drug, has recently been repurposed as a potential antimicrobial agent; it performed well against many Gram-positive bacteria, including multidrug resistant strains. It is, however, inactive toward Gram-negative bacteria, for which we are in dire need of new therapies. In this work, 40 auranofin analogues were synthesized by varying the structures of the thiol and phosphine ligands, and their activities were tested against ESKAPE pathogens. The study identified compounds that exhibited bacterial inhibition (MIC) and killing (MBC) activities up to 65 folds higher than that of auranofin, making them effective against Gram-negative pathogens. Both thiol and the phosphine structures influence the activities of the analogues. The trimethylphosphine and triethylphosphine ligands gave the highest activities against Gram-negative and Gram-positive bacteria, respectively. Our SAR study revealed that the thiol ligand is also very important, the structure of which can modulate the activities of the AuI complexes for both Gram-negative and Gram-positive bacteria. Moreover, these analogues had mammalian cell toxicities either similar to or lower than that of auranofin.
Combining Click Reactions for the One-Pot Synthesis of Modular Biomolecule Mimetics
Brink?, Anne,Risinger, Christian,Lambert, Annie,Blixt, Ola,Grandjean, Cyrille,Jensen, Henrik H.
supporting information, p. 7544 - 7548 (2019/10/08)
Here, we report on the first combined one-pot use of the two so-called "click reactions": The thiol-ene coupling and the copper-catalyzed alkyne-azide cycloaddition. These reactions were employed in an alternating and one-pot fashion to combine appropriately functionalized monomeric carbohydrate building blocks to create mimics of trisaccharides and tetrasaccharides as single anomers, with only minimal purification necessary. The deprotected oligosaccharide mimics were found to bind both plant lectins and human galectin-3.
Glycosyl triazoles as novel insect β-N-acetylhexosaminidase OfHex1 inhibitors: Design, synthesis, molecular docking and MD simulations
Dong, Lili,Shen, Shengqiang,Chen, Wei,Lu, Huizhe,Xu, Dongdong,Jin, Shuhui,Yang, Qing,Zhang, Jianjun
, p. 2315 - 2322 (2018/12/11)
The insect enzyme GH20 β-N-acetyl-D-hexosaminidase OfHex1 represents an important chitinolytic enzyme found in the agricultural pest Ostrinia furnacalis (Guenée) and inhibition of this enzyme has been considered a promising strategy for the development of eco-friendly pesticides. In this article, based on the structure of the catalytic domains of OfHex1, a series of novel glycosyl triazoles were designed and synthesized via Cu-catalyzed azide-alkyne [3+2] cycloaddition reaction. To investigate the potency and selectivity of these glycosyl triazoles, the inhibition activities towards OfHex1 and HsHexB (human β-N-acetylhexosaminidase B) were studied. Particularly compound 17c (OfHex1, Ki = 28.68 μM; HsHexB, Ki > 100 μM) exhibited a suitable activity and selectivity against OfHex1. Furthermore, the possible inhibitory mechanisms of 17c with OfHex1 were studied using molecular docking and MD simulations. The structure-activity relationship results as well as the formed binding patterns may provide promising insights into the further development of novel OfHex1 inhibitors.
Synthesis, Optimization, and Evaluation of Glycosylated Naphthalimide Derivatives as Efficient and Selective Insect β- N-Acetylhexosaminidase OfHex1 Inhibitors
Shen, Shengqiang,Dong, Lili,Chen, Wei,Wu, Renjie,Lu, Huizhe,Yang, Qing,Zhang, Jianjun
, p. 6387 - 6396 (2019/06/07)
Insect chitinolytic β-N-acetylhexosaminidase OfHex1, from the agricultural pest Ostrinia furnacalis (Guenée), is considered as a potential target for green pesticide design. In this study, rational molecular design and optimization led to the synthesis of compounds 15r (Ki = 5.3 μM) and 15y (Ki = 2.7 μM) that had superior activity against OfHex1 than previously reported lead compounds. Both compounds 15r and 15y had high selectivity toward OfHex1 over human β-N-acetylhexosaminidase B (HsHexB) and human O-GlcNAcase (hOGA). In addition, to investigate the basis for the potency of glycosylated naphthalimides against OfHex1, molecular docking and molecular dynamics simulations were performed to study possible binding modes. Furthermore, the in vivo biological activity of target compounds with efficient OfHex1 inhibitory potency was assayed against Myzus persicae, Plutella xylostella, and O. furnacalis. This present work indicates that glycosylated naphthalimides can be further developed as potential pest control and management agents targeting OfHex1.
Thioglycosides Are Efficient Metabolic Decoys of Glycosylation that Reduce Selectin Dependent Leukocyte Adhesion
Wang, Shuen-Shiuan,Gao, Xuefeng,Solar, Virginia del,Yu, Xinheng,Antonopoulos, Aristotelis,Friedman, Alan E.,Matich, Eryn K.,Atilla-Gokcumen, G. Ekin,Nasirikenari, Mehrab,Lau, Joseph T.,Dell, Anne,Haslam, Stuart M.,Laine, Roger A.,Matta, Khushi L.,Neelamegham, Sriram
, p. 1519 - 5,1532 (2018/10/24)
Small-molecule inhibitors of glycosylation can be applied in basic science studies, and clinical investigations as anti-inflammatory, anti-metastatic, and anti-viral therapies. This article demonstrates that thioglycosides represent a class of potent metabolic decoys that resist hydrolysis, and block E-selectin-dependent leukocyte adhesion in models of inflammation. Metabolic decoys are synthetic analogs of naturally occurring biosynthetic acceptors. These compounds divert cellular biosynthetic pathways by acting as artificial substrates that usurp the activity of natural enzymes. While O-linked glycosides are common, they are only partially effective even at millimolar concentrations. In contrast, we report that N-acetylglucosamine (GlcNAc) incorporated into various thioglycosides robustly truncate cell surface N- and O-linked glycan biosynthesis at 10–100 μM concentrations. The >10-fold greater inhibition is in part due to the resistance of thioglycosides to hydrolysis by intracellular hexosaminidases. The thioglycosides reduce β-galactose incorporation into lactosamine chains, cell surface sialyl Lewis-X expression, and leukocyte rolling on selectin substrates including inflamed endothelial cells under fluid shear. Treatment of granulocytes with thioglycosides prior to infusion into mouse inhibited neutrophil homing to sites of acute inflammation and bone marrow by ～80%–90%. Overall, thioglycosides represent an easy to synthesize class of efficient metabolic inhibitors or decoys. They reduce N-/O-linked glycan biosynthesis and inflammatory leukocyte accumulation.
