- Assembly, postsynthetic modification and hepatocyte targeting by multiantennary, galactosylated soft structures
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Enzyme modifiable, hollow self-assembled structures offer an excellent scope for multiantennary delivery vectors. Herein, we report synthesis and applications of bis-galactose lysine based supramolecular ensembles, which possess surface galactose moieties
- Thomas, Anisha,Shukla, Akansha,Sivakumar, Sri,Verma, Sandeep
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- Inhibition of pseudomonas aeruginosa biofilm formation with surface modified polymeric nanoparticles
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The gram-negative bacterial pathogen Pseudomonas aeruginosa represents a prominent clinical concern. Due to the observed high levels of antibiotic resistance, copious biofilm formation, and wide array of virulence factors produced by these bacteria, new treatment technologies are required. Here, we present the development of a series of P. aeruginosa LecA-targeted polymeric nanoparticles and demonstrate the anti-adhesion and biofilm inhibitory properties of these constructs.
- Flockton, Tyler R.,Schnorbus, Logan,Araujo, Agustin,Adams, Jill,Hammel, Maryjane,Perez, Lark J.
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- Size-optimized galactose-capped gold nanoparticles for the colorimetric detection of heat-labile enterotoxin at nanomolar concentrations
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The development of a galactose-capped gold nanoparticle-based colorimetric sensor for the detection of the lectin heat-labile enterotoxin is reported. Heat-labile enterotoxin is one of the pathogenic agents responsible for the intestinal disease called 'traveller's diarrhoea'. By means of specific interaction between galactose moieties attached to the surface of gold nanoparticles and receptors on the B-subunit of heat-labile enterotoxin (LTB), the gold nanoparticles reported here act as an efficient colorimetric sensor, which can detect the toxin at nanomolar concentrations. The effect of gold nanoparticle size on the detection sensitivity was investigated in detail. Amongst the various sizes of gold nanoparticles studied (2, 7, 12, and 20 nm), the 12 nm sized gold nanoparticles were found to be the most efficient, with a minimum heat-labile enterotoxin detection concentration of 100 nM. The red to purple colour change of the gold nanoparticle solution occurred within two minutes, indicating rapid toxin sensing. This journal is
- Poonthiyil, Vivek,Golovko, Vladimir B.,Fairbanks, Antony J.
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- Potent Glycosidase Inhibition with Heterovalent Fullerenes: Unveiling the Binding Modes Triggering Multivalent Inhibition
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Glycosidases are key enzymes in metabolism, pathogenic/antipathogenic mechanisms and normal cellular functions. Recently, a novel approach for glycosidase inhibition that conveys multivalent glycomimetic conjugates has emerged. Many questions regarding the mechanism(s) of multivalent enzyme inhibition remain unanswered. Herein we report the synthesis of a collection of novel homo- and heterovalent glyco(mimetic)-fullerenes purposely conceived for probing the contribution of non-catalytic pockets in glysosidases to the multivalent inhibitory effect. Their affinities towards selected glycosidases were compared with data from homovalent fullerene conjugates. An original competitive glycosidase–lectin binding assay demonstrated that the multivalent derivatives and the substrate compete for low affinity non-glycone binding sites of the enzyme, leading to inhibition by a “recognition and blockage” mechanism. Most notably, this work provides evidence for enzyme inhibition by multivalent glycosystems, which will likely have a strong impact in the glycosciences given the utmost relevance of multivalency in Nature.
- Abellán Flos, Marta,García Moreno, M. Isabel,Ortiz Mellet, Carmen,García Fernández, Jose Manuel,Nierengarten, Jean-Francois,Vincent, Stéphane P.
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- Synthesis, anticancer activity and cytotoxicity of 7-O-β-d-galactosyl-polyethylene glycol-epothilone B
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Epothilone, the macrolide compound produced by Sorangium cellulosum, has antitumor activity. Its anti-tumor mechanism is similar to that of paclitaxel, which promotes the polymerization of tubulin and induces apoptosis. Herein, 7-O-β-d-galactosyl-polyethy
- Huang, Shiyu,Huang, Gangliang
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- A spontaneous single-crystal-to-single-crystal polymorphic transition involving major packing changes
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4,6-O-Benzylidene-α-d-galactosyl azide crystallizes into two morphologically distinct polymorphs depending on the solvent. While the α form appeared as thick rods and crystallized in P21 space group (monoclinic) with a single molecule in the asymmetric unit, the β form appeared as thin fibers and crystallized in P1 space group (triclinic) with six molecules in the asymmetric unit. Both the polymorphs appeared to melt at the same temperature. Differential scanning calorimetry analysis revealed that polymorph α irreversibly undergoes endothermic transition to polymorph β much before its melting point, which accounts for their apparently same melting points. Variable temperature powder X-ray diffraction (PXRD) experiments provided additional proof for the polymorphic transition. Single-crystal XRD analyses revealed that α to β transition occurs in a single-crystal-to-single-crystal (SCSC) fashion not only under thermal activation but also spontaneously at room temperature. The SCSC nature of this transition is surprising in light of the large structural differences between these polymorphs. Polarized light microscopy experiments not only proved the SCSC nature of the transition but also suggested nucleation and growth mechanism for the transition.
- Krishnan, Baiju P.,Sureshan, Kana M.
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- Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity
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Tacrine is a known Acetylcholinesterase (AChE) inhibitors having hepatotoxicity as main liability associated with it. The present study aims to reduce its hepatotoxicity by synthesizing tacrine linked triazole glycoconjugates via Huisgen's [3 + 2] cycloaddition of anomeric azides and terminal acetylenes derived from tacrine. A series of triazole based glycoconjugates containing both acetylated (A-1 to A-7) and free sugar hydroxyl groups (A-8 to A-14) at the amino position of tacrine were synthesized in good yield taking aid from molecular docking studies and evaluated for their in vitro AChE inhibition activity as well as hepatotoxicity. All the hybrids were found to be non-toxic on HePG2 cell line at 200 μM (100 % cell viability) as compared to tacrine (35 % cell viability) after 24 h of incubation period. Enzyme kinetic studies carried out for one of the potent hybrids in the series A-1 (IC50 0.4 μM) revealed its mixed inhibition approach. Thus, compound A-1 can be used as principle template to further explore the mechanism of action of different targets involved in Alzheimer's disease (AD) which stands as an adequate chemical probe to be launched in an AD drug discovery program.
- Kaur Gulati, Harmandeep,Choudhary, Sushil,Kumar, Nitish,Ahmed, Ajaz,Bhagat, Kavita,Vir Singh, Jatinder,Singh, Atamjit,Kumar, Ajay,Singh Bedi, Preet Mohinder,Singh, Harbinder,Mukherjee, Debaraj
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- Selectivity of 1-O-Propargyl-D-Mannose Preparations
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Thanks to their ability to bind to specific biological receptors, mannosylated structures are examined in biomedical applications. One of the most common ways of linking a functional moiety to a structure is to use an azide-alkyne click reaction. Therefore, it is necessary to prepare and isolate a propargylated mannose derivative of high purity to maintain its bioactivity. Three known preparations of propargyl-α-mannopyranoside were revisited, and products were analysed by NMR spectroscopy. The preparations were shown to yield by-products that have not been described in the literature yet. Our experiments showed that one-step procedures could not provide pure propargyl-α-mannopyranoside, while a three-step procedure yielded the desired compound of high purity.
- ?ezanka, Michal,Dolensky, Bohumil,Krabicová, Ilona
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- PROCESS OF SYNTHESIS OF β-6'SULFOQUINOVOSYL DIACYLGLYCEROLS
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The present invention relates to a synthesis process of β-6-sulfoquinovosyl-diacylglycerols. In particular, said process is for the synthesis of the compounds 1,2-O-distearoyl-3-O-(β- sulfoquinovosyl)-R/S-glycerol, 1,2-O-distearoyl-3-O-(β-sulfoquinovosyl)-R-glycerol or 1,2- O-distearoyl-3-O-(β-sulfoquinovosyl)-S-glycerol, named respectively Sulfavant A, Sulfavant R and Sulfavant S.
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(2022/02/28)
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- Synthesis and biological evaluation of 3β-O-neoglycosides of caudatin and its analogues as potential anticancer agents
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In order to study the structure–activity relationship (SAR) of C21-steroidal glycosides toward human cancer cell lines and explore more potential anticancer agents, a series of 3β-O-neoglycosides of caudatin and its analogues were synthesized. The results revealed that most of peracetylated 3β-O-monoglycosides demonstrated moderate to significant antiproliferative activities against four human cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, 3β-O-(2,3,4-tri-O-acetyl-β-L-glucopyranosyl)-caudatin (2k) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC50 value of 3.11 μM. Mechanical studies showed that compound 2k induced both apoptosis and cell cycle arrest at S phase in a dose dependent manner. Overall, these present findings suggested that glycosylation is a promising scaffold to improve anticancer activity for naturally occurring C21-steroidal aglycones, and compound 2k represents a potential anticancer agent deserved further investigation.
- Li, Xiao-San,Chen, Tang-Ji,Xu, Zhi-Peng,Long, Juan,He, Miao-Ying,Zhan, He-Hui,Zhuang, Hai-Cai,Wang, Qi-Lin,Liu, Li,Yang, Xue-Mei,Tang, Jin-Shan
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- Pillar[5]arene-Based Polycationic Glyco[2]rotaxanes Designed as Pseudomonas aeruginosa Antibiofilm Agents
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Pseudomonas aeruginosa (P.A.) is a human pathogen belonging to the top priorities for the discovery of new therapeutic solutions. Its propensity to generate biofilms strongly complicates the treatments required to cure P.A. infections. Herein, we describe the synthesis of a series of novel rotaxanes composed of a central galactosylated pillar[5]arene, a tetrafucosylated dendron, and a tetraguanidinium subunit. Besides the high affinity of the final glycorotaxanes for the two P.A. lectins LecA and LecB, potent inhibition levels of biofilm growth were evidenced, showing that their three subunits work synergistically. An antibiofilm assay using a double δlecAδlecB mutant compared to the wild type demonstrated that the antibiofilm activity of the best glycorotaxane is lectin-mediated. Such antibiofilm potency had rarely been reached in the literature. Importantly, none of the final rotaxanes was bactericidal, showing that their antibiofilm activity does not depend on bacteria killing, which is a rare feature for antibiofilm agents.
- Coenye, Tom,De Winter, Julien,Diaconu, Andrei,Fransolet, Maude,Gillon, Emilie,Imberty, Anne,Jimmidi, Ravikumar,Michiels, Carine,Mohy El Dine, Tharwat,Vincent, Stéphane P.
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supporting information
p. 14728 - 14744
(2021/10/12)
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- New amphiphilic platinum(II) phthalocyanine with peracetylated β-galactose moiety – Synthesis and photophysical properties
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The synthesis of new glycoconjugated phthalonitrile connected with galactose moiety by triazole spacer via Cu(II)-mediated click reaction is reported. Reaction of azido derivatives of. β-D-galactopyranose tetraacetate with 4-O-propargyloxy-substituted phthalonitrile in presence copper(II) sulfate pentahydrate and sodium L-ascorbate in tert-butanol/water gave desired glycophthalonitrile with 79% yield. Obtained phthalonitrile underwent mixed-cyclisation with the 4-tert-butyl-substituted phthalonitrile, to afford the mono-glycosylated platinum(II) phthalocyanine. Upon irradiation these compounds could sensitise the formation of singlet oxygen in acetone, with 0.90 quantum yield by method with use of 1,3-diphenylisobenzofuran (DPBF) as scavenger.
- Burtsev, Ivan D.,Volov, Alexander N.,Volov, Nikolai A.
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- Galactose-clicked curcumin-mediated reversal of meropenem resistance among klebsiella pneumoniae by targeting its carbapenemases and the AcrAB-TolC efflux system
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In over eighty years, despite successive antibiotics discoveries, the rapid advent of multidrug resistance among bacterial pathogens has jolted our misapprehension of success over them. Resistance is spreading faster than the discovery of new antibiotics/antimicrobials. Therefore, the search for better antimicrobials/additives becomes prudent. A water-soluble curcumin derivative (Curaq) was synthesised, employing a Cu (I) catalysed 1, 3-cyclo addition reaction; it has been evaluated as a potential treatment for multidrug-resistant isolates and as an antibiotic adjuvant for meropenem against hypervirulent multidrug-resistant Klebsiella pneumoniae isolates. We also investigated its solubility and effect over carbapenemase activity. Additionally, we investigated its impact on the AcrAB-TolC system. We found that Curaq inhibited bacterial growth at a minimal concentration of 16 ug/mL; at a 32 ug/mL concentration, it killed bacterial growth completely. Only nine (9.4%) Klebsiella isolates were sensitive to meropenem; however, after synergising with Curaq (8 ug/mL), 85 (88.54%) hvKP isolates became sensitive to the drug. The Curaq also inhibited the AcrAB-TolC efflux system at 1 ug/mL concentration by disrupting the membrane potential and causing depolarisation. The kinetic parameters obtained also indicated its promise as a carbapenemase inhibitor. These results suggest that Curaq can be an excellent drug candidate as a broad-spectrum antibacterial and anti-efflux agent.
- Yadav, Shivangi,Singh, Ashish Kumar,Agrahari, Anand K.,Pandey, Akhilesh Kumar,Gupta, Munesh Kumar,Chakravortty, Dipshikha,Tiwari, Vinod Kumar,Prakash, Pradyot
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- GLYCOSIDE COMPOUND AND PREPARATION METHOD THEREFOR, COMPOSITION, APPLICATION, AND INTERMEDIATE
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The present invention discloses a glycoside compound represented by Formula III, and a preparation method, a composition, use and an intermediate thereof. The glycoside compound provided in the present invention has simple preparation method, can significantly increase the expression of VEGF-A mRNA, and is effective in promoting the angiogenesis. This provides a reliable guarantee for the development of drugs with pro-angiogenic activity for treating cerebral infarction cerebral stroke, myocardial infarction, and ischemic microcirculatory disturbance of lower limbs.
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Paragraph 0335-0337
(2021/04/23)
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- Efficient and reproducible synthesis of an Fmoc-protected Tn antigen
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This concise total synthesis of the Thomsen-Nouveau (Tn) glycoconjugate was accomplished using a palladium-catalyzed coupling between the glycosyl donor and Fmoc-protected serine acceptor. This is, to the best of our knowledge, the shortest synthesis reported from galactose for preparing this essential building block for large-scale solid phase peptide synthesis.
- Chapa-Villarreal, Fabiola A.,Chiaramonte, Jonathan,Piazza, Sabrina M.,Reynolds, Michael R.,Trant, John F.,Xu, Peihan
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supporting information
p. 19224 - 19227
(2021/11/09)
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- CuAAC mediated synthesis of cyclen cored glycodendrimers of high sugar tethers at low generation
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Glycodendrimers are receiving considerable attention to mimic a number of imperative features of cell surface glycoconjugate and acquired excellent relevance to a wide domain of investigations including medicine, pharmaceutics, catalysis, nanotechnology, carbohydrate-protein interaction, and moreover in drug delivery systems. Toward this end, an expeditious, modular, and regioselective triazole-forming CuAAC click approach along with double stage convergent synthetic method was chosen to develop a variety of novel chlorine-containing cyclen cored glycodendrimers of high sugar tethers at low generation of promising therapeutic potential. We developed a novel chlorine-containing hypercore unit with 12 alkynyl functionality originated from cyclen scaffold which was confirmed by its single crystal X-ray data analysis. Further, the modular CuAAC technique was utilized to produce a variety of novel 12–sugar coated (G0) glycodendrimers 12-15 adorn with β-Glc-, β-Man-, β-Gal-, β-Lac, along with 36-galactose coated (G1) glycodendrimer 18 in good-to-high yield. The structures of the developed glycodendrimer architectures have been well elucidated by extensive spectral analysis including NMR (1H & 13CNMR), HRMS, MALDI-TOF MS, UV–Vis, IR, and SEC (Size Exclusion Chromatogram) data.
- Agrahari, Anand K.,Jaiswal, Manoj K.,Yadav, Mangal S.,Tiwari, Vinod K.
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- Synthesis of Glycosyl Fluorides by Photochemical Fluorination with Sulfur(VI) Hexafluoride
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This study describes a new convenient method for the photocatalytic generation of glycosyl fluorides using sulfur(VI) hexafluoride as an inexpensive and safe fluorinating agent and 4,4′-dimethoxybenzophenone as a readily available organic photocatalyst. This mild method was employed to generate 16 different glycosyl fluorides, including the substrates with acid and base labile functionalities, in yields of 43%-97%, and it was applied in continuous flow to accomplish fluorination on an 7.7 g scale and 93% yield.
- Bannykh, Anton,Khomutnyk, Yaroslav,Kim, Sungjin,Nagorny, Pavel
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supporting information
p. 190 - 194
(2021/01/13)
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- BIVALENT LECA INHIBITORS TARGETING BIOFILM FORMATION OF PSEUDOMONAS AERUGINOSA
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The present invention relates to divalent compounds binding to LecA. The compounds are useful to block biofilm formation of Pseudomonas aeruginosa. The invention further relates to pharmaceutical compositions comprising these compounds and to therapeutic methods and uses of these compounds, in particular to therapeutic methods and uses for the treatment of Pseudomonas aeruginosa infections in a subject. The invention also relates to imaging of infections, such as biofilms produced by Pseudomonas aeruginosa, by using these divalent compounds.
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Page/Page column 28; 42
(2021/05/15)
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- Protecting carbohydrates with ethers, acetals and orthoesters under basic conditions
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Chlorinated ethyl and vinyl ethers are introduced at various positions of carbohydrates. Depending on the relative stereochemistry, vinylethers, acetals or orthoesters are formed under basic conditions. The products are stable, but are easily deprotected
- Liang, Yang,Pedersen, Christian M.
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supporting information
p. 7598 - 7601
(2021/09/22)
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- A Sweet H2S/H2O2Dual Release System and Specific Protein S-Persulfidation Mediated by Thioglucose/Glucose Oxidase
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H2S and H2O2 are two redox regulating molecules that play important roles in many physiological and pathological processes. While each of them has distinct biosynthetic pathways and signaling mechanisms, the crosstalk between these two species is also known to cause critical biological responses such as protein S-persulfidation. So far, many chemical tools for the studies of H2S and H2O2 have been developed, such as the donors and sensors for H2S and H2O2. However, these tools are normally targeting single species (e.g., only H2S or only H2O2). As such, the crosstalk and synergetic effects between H2S and H2O2 have hardly been studied with those tools. In this work, we report a unique H2S/H2O2 dual donor system by employing 1-thio-β-d-glucose and glucose oxidase (GOx) as the substrates. This enzymatic system can simultaneously produce H2S and H2O2 in a slow and controllable fashion, without generating any bio-unfriendly byproducts. This system was demonstrated to cause efficient S-persulfidation on proteins. In addition, we expanded the system to thiolactose and thioglucose-disulfide; therefore, additional factors (β-galactosidase and cellular reductants) could be introduced to further control the release of H2S/H2O2. This dual release system should be useful for future research on H2S and H2O2.
- Ni, Xiang,Li, Xiaolu,Shen, Tun-Li,Qian, Wei-Jun,Xian, Ming
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supporting information
p. 13325 - 13332
(2021/09/03)
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- Chemical Synthesis and Biological Evaluations of Adiponectin Collagenous Domain Glycoforms
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The homogeneously glycosylated 76-amino acid adiponectin collagenous domains (ACDs) with all of the possible 15 glycoforms have been chemically and individually synthesized using stereoselective glycan synthesis and chemical peptide ligation. The following biological and pharmacological studies enabled correlating glycan pattern to function in the inhibition of cancer cell growth as well as the regulation of systemic energy metabolism. In particular, hAdn-WM6877 was tested in detail with different mouse models and it exhibited promising in vivo antitumor, insulin sensitizing, and hepatoprotective activities. Our studies demonstrated the possibility of using synthetic glycopeptides as the adiponectin downsized mimetic for the development of novel therapeutics to treat diseases associated with deficient adiponectin.
- Wu, Hongxiang,Zhang, Yiwei,Li, Yuanxin,Xu, Jianchao,Wang, Yu,Li, Xuechen
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supporting information
p. 7808 - 7818
(2021/05/26)
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- Total synthesis of three natural phenethyl glycosides
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Phenethyl glycosides having phenolic or methoxy functions at benzene rings are substances widely occurring in nature. This kind of compounds has been shown to have anti-oxidant, anti-inflammatory, and anticancer activities. However, some of them are not naturally abundant, thus the synthesis of such molecules is desirable. In this paper, natural phenethyl glycosides 3 and 4 were first totally synthesized from easily available materials with overall yields of 50.5% and 40.1%, respectively. And a new synthetic route to obtain natural phenethyl glycoside 2 in 46.2% yield was also described.
- Dong, Hong-Bo,Meng, Jian,Yao, Zhong-Quan,Luo, Hong-Bing,Zhang, Jing-Xia,Du, Wei-Hong,Tang, Ke-Hui,Cao, Sheng-Hua
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p. 284 - 293
(2020/03/03)
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- An alternative approach for the synthesis of sulfoquinovosyldiacylglycerol
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Sulfoquinovosyldiacylglycerol (SQDG) is a glycolipid ubiquitously found in photosyn-thetically active organisms. It has attracted much attention in recent years due to its biological ac-tivities. Similarly, the increasing demand for vegan and functional foods has led to a growing interest in micronutrients such as sulfolipids and their physiological influence on human health. To study this influence, reference materials are needed for developing new analytical methods and providing enough material for model studies on the biological activity. However, the availability of these materials is limited by the difficulty to isolate and purify sulfolipids from natural sources and the unavailability of chemical standards on the market. Consequently, an alternative synthetic route for the comprehensive preparation of sulfolipids was established. Here, the synthesis of a sulfolipid with two identical saturated fatty acids is described exemplarily. The method opens possibilities for the preparation of a diverse range of interesting derivatives with different saturated and unsatu-rated fatty acids.
- Domey, Hendrik,Fischer, Judith,Rohn, Sascha,Sitz, Tobias
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- First total syntheses of two natural glycosides
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Isosyringinoside (1) and 3-(O-β-D-glucopyranosyl)-α-(O-β-D-glucopyranosyl)-4-hydroxy phenylethanol (2), the natural bioactive compounds contained unique structures, were first totally synthesized using easily available materials in short convenient routes with overall yields of 20.2% and 27.0%, respectively. An efficient total synthesis of 1 was developed in six steps, which contained two key steps of highly regioselective glycosylation without any selective protection steps. The seven-step synthesis of 2 involved two steps of regioselective glycosylations using BF3–O(C2H5)2 and TMSOTf as catalysts, respectively.
- Dong, Hongbo,Du, Weihong,Yao, Zhongquan,Wu, Min,Luo, Hongbing,He, Yujiao,Cao, Shenghua
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supporting information
(2020/12/02)
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- Preparation and formulation optimization of methotrexate-loaded human serum albumin nanoparticles modified by mannose
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Background: Methotrexate (MTX) is the representative drug among the dis-ease-modifying anti-rheumatic drugs. However, the conventional treatment with MTX showed many limitations and side effects. Objective: To strengthen the targeting ability and circulation time of MTX in the treatment of rheumatoid arthritis, the present study focused on developing a novel drug delivery system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified by mannose, which are referred to as MTX-M-NPs. Methods: Firstly, mannose-derived carboxylic acid was synthesized and further modified on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles was optimized by the method of central composite design (CCD), with the drug lipid ra-tio, oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The average particle size and encapsulation efficiency were the response variables. The response of different formulations was calculated, and the response surface diagram, con-tour diagram, and mathematical equation were used to relate the dependent and independent variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neu-trophils was studied through confocal laser detection. Further, MTX-M-NPs were subject-ed to assessment of the pharmacokinetics profile after intravenous injection with Sprague-Dawley rats. Results: This targeting drug delivery system was successfully developed. Results from Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can verify the successful preparation of this drug delivery system. Based on the optimized for-mula, MTX-M-NPs were prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could pro-long the in vivo circulation time of MTX. Conclusion: This targeting drug delivery system laid a promising foundation for the treatment of RA.
- Chen, Zhenyu,Luo, Zhongling,Lyu, Jiayao,Wang, Jianxin,Liu, Zhongbing,Wei, Jun,Lin, Yan,Zhong, Zhirong
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p. 5016 - 5029
(2021/08/17)
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- Does targeting Arg98 of FimH lead to high affinity antagonists?
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Bacterial resistance has become an important challenge in the treatment of urinary tract infections. The underlying resistance mechanisms can most likely be circumvented with an antiadhesive approach, antagonizing the lectin FimH located at the tip of fim
- Toma?i?, Tihomir,Rabbani, Said,Jakob, Roman P.,Reisner, Andreas,Jakopin, ?iga,Maier, Timm,Ernst, Beat,Anderluh, Marko
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- Amino acid derivative and preparation method thereof
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The invention discloses an amino acid derivative and a preparation method thereof. The amino acid comprises - SH and/or - OH groups, wherein the sugar chain comprises one mannose or more than two mannose in series, and the linker comprises S or o, the method of the invention can synthesize the required polysaccharide compound in one step, thereby not only saving a large amount of manpower and time, but also enabling a large amount of preparation of the target compound to be smooth. , The synthesis yield of the product is improved, a large amount of synthetic raw materials are saved, the production cost is greatly reduced, meanwhile, the environmental protection is facilitated, and the research of amino acid glycosylation is broken through and the application barrier is applied.
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Paragraph 0056-0060
(2021/10/11)
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- Preparation and characterization of glycopolymers with biphenyl spacers: Via Suzuki coupling reaction
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Poly(vinylbiphenyl)s bearing glycoside ligands at the side chains were prepared using the Suzuku coupling reaction. Effects of glycoside reactant concentration, halide species, glycoside species, and catalyst species on the incorporation of glycoside ligand into the polymer were investigated. The obtained glycopolymers exhibited specific binding to proteins corresponding to the glycoside ligands. In addition, the biphenyl spacers formed by the Suzuki coupling reaction in the glycopolymer were fluorescent, whereas the polymer precursor was not.
- Seto, Hirokazu,Tono, Takumi,Nagaoka, Akiko,Yamamoto, Mai,Hirohashi, Yumiko,Shinto, Hiroyuki
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supporting information
p. 4474 - 4477
(2021/05/31)
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- Isolation and characterization of triterpenoid saponins from leaves of Aralia nudicaulis L
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Three new oleanolic glycosides (1–3), along with seven known saponins from various plants (4–10) were isolated for the first time from the leaves of Aralia nudicaulis. Their structures were elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR, and HRESIMS. Nudicauloside A and B (1–2) have shown moderate anti-inflammatory activity, as demonstrated by inhibition of LPS-induced NO production in raw 264.7 murine macrophages (IC50 = 74–101 μM).
- Lavoie, Serge,Pierra, Julie,Legault, Jean,Raminoson, Diamondra,Lion, Quentin,Mshvildadze, Vakhtang,Pichette, André
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p. 184 - 189
(2021/04/23)
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- First total syntheses of four natural bioactive glucosides
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The efficient total syntheses of four biologically interesting natural glucosides Ethylconiferin, Butylconiferin, 2’-Butoxyethylconiferin and Balajaponin B, have been achieved for the first time starting from commercially available Vanilline via concise reaction sequence of 8–10 steps with the overall yield of 26–41%. This work definitely laid the foundation for the further pharmacological study of this kind of natural compounds. Meanwhile, currently developed approach could be used as a general synthetic strategy for the syntheses of other monolignol glucosides and their derivatives, and provides an opportunity for further study of the structure-activity relationship of this kind of glucosides.
- Xu, Guangya,Wu, Min,Yao, Zhongquan,Lou, Hongbin,Du, Weihong,Song, Mingwei,He, Yujiao,Dong, Hongbo
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supporting information
p. 1266 - 1271
(2021/02/06)
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- Inhibition of S. aureus Infection of Human Umbilical Vein Endothelial Cells (HUVECs) by Trehalose- and Glucose-Functionalized Gold Nanoparticles
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Microbial adhesion to host cells represents the initial step in the infection process. Several methods have been explored to inhibit microbial adhesion including the use of glycopolymers based on mannose, galactose, sialic acid and glucose. These sugar re
- Li, Yimeng,Ariotti, Nicholas,Aghaei, Behnaz,Pandzic, Elvis,Ganda, Sylvia,Willcox, Mark,Sanchez-Felix, Manuel,Stenzel, Martina
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supporting information
p. 22652 - 22658
(2021/09/13)
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- Mannose-modified azide exosome and application thereof
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The invention belongs to the field of biological medicine, and particularly relates to a mannose-modified azide exosome and an application thereof. The mannose-modified azide exosome is prepared through metabolic labeling and click chemistry reaction; the advantages of the surface-functionalized azide exosome targeting macrophages are determined through a flow cytometry on the cellular level, and in-vitro pharmacological experiments prove that the mannose-modified azide exosome has the advantage of treating infectious diseases after being loaded with drugs. According to the surface-functionalized azide exosome provided by the invention, the targeting property of the exosome as a drug carrier can be greatly improved, and the effect of the surface-functionalized azide exosome in treating refractory infectious related diseases is improved.
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Paragraph 0056; 0062-0064
(2021/06/23)
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- Anti-tick-borne encephalitis virus activity of novel uridine glycoconjugates containing amide or/and 1,2,3-triazole moiety in the linker structure
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Tick-borne encephalitis virus (TBEV) transmitted by ticks is a pathogen of great medical importance. As still no effective antiviral treatment is available, in the present study, a series of uridine glycoconjugates containing amide or/and 1,2,3-triazole moiety in the linker structure was synthesized and evaluated for the antiviral activity against two strains of TBEV: a highly virulent Hypr strain and less virulent Neudoerfl strain, using standardized previously in vitro assays. Our data have shown that four compounds from the series (18–21) possess strong activity against both TBEV strains. The half maximal inhibitory concentration (IC50) values of compounds 18–21 were between 15.1 and 3.7 μM depending on the virus strain, which along with low cytotoxicity resulted in high values of the selectivity index (SI). The obtained results suggest that these compounds may be promising candidates for further development of new therapies against flaviviruses.
- Brzuska, Gabriela,Pastuch-Gawolek, Gabriela,Krawczyk, Monika,Szewczyk, Boguslaw,Krol, Ewelina
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- Synthesis of glycoimmunogen Tn-Thr-PS A1 via hydrazone bond and stability optimization of PS A1 monosaccharide mimics under vaccine development conditions
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Previously, our group constructed several immunogens utilizing oxime linkage to conjugate a T-cell stimulatory zwitterionic polysaccharide PS A1 and tumor associated carbohydrate antigens (TACAs) in acetate buffer. Here, a semi-synthetic immunogen was synthesized using hydrazone conjugation between PS A1 and a glycopeptide hydrazide (α-D-GalNAc-L-Thr-NH-NH2) with an excellent loading in PBS buffer. To get robust immune response, the retention of zwitterionic character of PS A1 under vaccine construction conditions is essential. In this regard, the stability of embedded pyruvate acetal moiety in tetrasaccharide repeating unit of PS A1 can validate the retention of the dual charges. Therefore, rather than utilizing this highly immunogenic PS A1 fully, stability studies were performed with synthetic 1-thiophenyl-4,6-O-pyruvate acetal-D-galactopyranose in varying acetate buffer pHs and time intervals. Furthermore, 1-propyl-D-galactofuranose was synthesized to mimick the D-Galf of PS A1 to examine regioselective hydrazone and oxime formation with α-D-GalNAc-L-Thr-NH-NH2 and α-D-GalNAc-ONH2 moieties respectively.
- Hossain,Nishat,Ghosh,Boga,Hymel,Andreana
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p. 107 - 129
(2020/02/11)
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- 8-Hydroxyquinoline glycoconjugates containing sulfur at the sugar anomeric position—synthesis and preliminary evaluation of their cytotoxicity
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One of the main factors limiting the effectiveness of many drugs is the difficulty of their delivery to their target site in the cell and achieving the desired therapeutic dose. Moreover, the accumulation of the drug in healthy tissue can lead to serious side effects. The way to improve the selectivity of a drug to the cancer cells seems to be its conjugation with a sugar molecule, which should facilitate its selective transport through GLUT transporters (glucose transporters), whose overexpression is seen in some types of cancer. This was the idea behind the synthesis of 8-hydroxyquinoline (8-HQ) derivative glycoconjugates, for which 1-thiosugar derivatives were used as sugar moiety donors. It was expected that the introduction of a sulfur atom instead of an oxygen atom into the anomeric position of the sugar would increase the stability of the obtained glycoconjugates against untimely hydrolytic cleavage. The anticancer activity of new compounds was determined based on the results of the MTT cytotoxicity tests. Because of the assumption that the activity of this type of compounds was based on metal ion chelation, the effect of the addition of copper ions on cell proliferation was tested for some of them. It turned out that cancer cells treated with glycoconjugates in the presence of Cu2+ had a much slower growth rate compared to cells treated with free glycoconjugates in the absence of copper. The highest cytotoxic activity of the compounds was observed against the MCF-7 cell line.
- Erfurt, Karol,Hadasik, Agnieszka,Krawczyk, Monika,Pastuch-Gawo?ek, Gabriela
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- Folding control of a non-natural glycopeptide using saccharide-coded structural information for polypeptides
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We synthesized "glyco-arylopeptides", whose folding structure significantly changes depending on the kind of saccharide in their side chain. The saccharide moiety interacts with the main chain via hydrogen bonding, and the non-natural polypeptides form two well-defined architectures - (P)-31- and (M)-41-helices - depending on the length of the saccharide chains and even the configuration of a single stereo-genic center in the epimers.
- Fujii, Naoka,Haino, Takeharu,Ishido, Yuki,Kanbayashi, Naoya,Okamura, Taka-Aki,Onitsuka, Kiyotaka
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supporting information
p. 2767 - 2770
(2020/03/13)
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- Preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant S
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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.
- Manzo, Emiliano,Fioretto, Laura,Gallo, Carmela,Ziaco, Marcello,Nuzzo, Genoveffa,D’Ippolito, Giuliana,Borzacchiello, Assunta,Fabozzi, Antonio,de Palma, Raffaele,Fontana, Angelo
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- Short gram-scale synthesis of sulfavant A
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Recently, we reported the promising activity of a novel class of sulfoquinovosyl-diacylglycerols named Sulfavants as molecular vaccine adjuvants. Herein, we describe a modified and improved chemical synthesis of the lead product Sulfavant A (1), with the aim to produce from milligrams to 10 g of the pure compound that is necessary for the preclinical development. Starting from the versatile synthesis based on the trichloroacetimidate methodology, up-scaled preparation of Sulfavant A (1) was achieved in 11 steps by elimination and modification of those reactions that negatively affected the overall yield by the previous procedure. The novel strategy gave 17% overall yield of the target compound 1 and also paved the way for the gram-scale preparation of a wide range of other charged and neutral glycoglycerolipids.
- Ziaco, Marcello,Fioretto, Laura,Nuzzo, Genoveffa,Fontana, Angelo,Manzo, Emiliano
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p. 2728 - 2733
(2020/11/18)
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- Tea leaf perfumery precursor glucoside and synthesizing method thereof
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The invention relates to a tea leaf perfumery precursor glucoside and a synthesizing method thereof. The synthesizing method comprises the following steps of synthesizing ten glucosides including aromatic alcohol ( alkanol )-beta -D-glucosides and aromatic alcohol (alkanol )-beta -D-primrose indicans. The synthesizing method disclosed by the invention is a glucoside synthesizing method which is good in selectivity, high in production rate and low in cost.
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Paragraph 0044-0049
(2020/07/02)
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- Carbonyl compound containing amino acid connecting chain or pharmaceutically acceptable salt thereof, and preparation method and application of carbonyl compound
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The invention provides a carbonyl compound containing an amino acid connecting chain or a pharmaceutically acceptable salt thereof as well as a preparation method and application of the carbonyl compound, and belongs to the technical field of anti-AIDS medicines. The carbonyl compound containing the amino acid connecting chain or the pharmaceutically acceptable salt thereof provided by the invention has a structure shown as formula I in the specification. The carbonyl compound containing the amino acid connecting chain or the pharmaceutically acceptable salt thereof provided by the inventionhas obvious activity of inhibiting HIV protease; the obvious inhibition activity is realized on the DRV drug-resistant strain; toxicity research shows that the compound is low in toxicity and has gooddruggability; the inhibitory activity on HIV-1 protease is 286-1052 times of the inhibitory activity of a positive control drug DRV on HIV-1 protease; the inhibitory activity on a DRV drug-resistantstrain and the inhibitory activity on a wild HIV-1 drug-resistant strain are only reduced by 1.10-3.23 times, and the compound has a good application prospect as an anti-AIDS drug.
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Paragraph 0215; 0224-0226
(2020/06/16)
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- Total Synthesis of Phospholipomannan of Candida albicans
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First, total synthesis of the cell surface phospholipomannan anchor [β-Manp-(1 → 2)-β-Manp]n-(1 → 2)-β-Manp-(1 → 2)-α-Manp-1 → P-(O → 6)-α-Manp-(1 → 2)-Inositol-1-P-(O → 1)-phytoceramide of Candida albicans is reported. The target phospholipomannan (PLM) anchor poses synthetic challenges such as the unusual kinetically controlled (1 → 2)-β-oligomannan domain, anomeric phosphodiester, and unique phytoceramide lipid tail linked to the glycan through a phosphate group. The synthesis of PLM anchor was accomplished using a convergent block synthetic approach using three main appropriately protected building blocks: (1 → 2)-β-tetramannan repeats, pseudodisaccharide, and phytoceramide-1-H-phosphonate. The most challenging (1 → 2)-β-tetramannan domain was synthesized in one pot using the preactivation method. The phytoceramide-1-H-phosphonate was synthesized through an enantioselective A3 three-component coupling reaction. Finally, the phytoceramide-1-H-phosphonate moiety was coupled with pseudodisaccharide followed by deacetylation to produce the acceptor, which on subsequent coupling with tetramannosyl-H-phosphonate provided the fully protected PLM anchor. Final deprotection was successfully achieved by Pearlman's hydrogenation.
- Ali, Asif,Gannedi, Veeranjaneyulu,Singh, Parvinder Pal,Vishwakarma, Ram A.
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p. 7757 - 7771
(2020/07/25)
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- Substituted pyrazole compound, preparation method, pharmaceutical composition and applications thereof
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The invention discloses a substituted pyrazole compound represented by a formula I, and a preparation method, a pharmaceutical composition and applications thereof, wherein the compound has characteristics of good stability, excellent solubility, low cytotoxicity and remarkable neuroprotective effect, can effectively prevent and treat nerve cell injury, and is an ideal medicinal compound for preventing or treating cerebral stroke, cerebral embolism, cerebral stroke sequelae, cerebral stroke dyskinesia, mitochondrial encephalomyopathy and amyotrophic lateral sclerosis of spinal cord.
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Paragraph 0299-0303
(2020/03/12)
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- Synthesis of C-Glycosyl Amino Acid Building Blocks Suitable for the Solid-Phase Synthesis of Multivalent Glycopeptide Mimics
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Five C-glycosyl functionalized lysine building blocks, featuring C-glycosidic derivatives of α-rhamnose, α-mannose, α-galactose, β-galactose, and β-N-acetyl glucosamine have been designed and synthesized. These derivatives, equipped with acid-labile protecting groups, are eminently suitable for solid-phase synthesis of multivalent glycopeptides. The lysine building blocks were prepared from C-allyl glycosides that underwent a Grubbs cross-metathesis with an acrylate, followed by a reduction of the C=C double bond in the resulting α,β-unsaturated esters, and liberation of the carboxylate to allow condensation with a lysine side chain. The thus obtained C-glycosides, five in total, were applied in the solid-phase peptide synthesis (SPPS) of three glycopeptides, showing the potential of the described building blocks in the assembly of well-defined mimics of homo- and heteromultivalent glycopeptides and glycoclusters.
- Reintjens, Niels R. M.,Koemans, Tony S.,Zilverschoon, Nick,Castelli, Riccardo,Cordfunke, Robert A.,Drijfhout, Jan Wouter,Meeuwenoord, Nico J.,Overkleeft, Herman S.,Filippov, Dmitri V.,van der Marel, Gijsbert A.,Codée, Jeroen D. C.
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supporting information
p. 5126 - 5139
(2020/06/23)
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- Tumor microenvironment responsive supramolecular glyco-nanovesicles based on diselenium-bridged pillar[5]arene dimer for targeted chemotherapy
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Supramolecular glyco-nanovesicles (SeSe-(P5)2?Man-NH3+) based on the host-guest complex of a diselenium-bridged pillar[5]arene dimer and a mannose derivative have been successfully developed for the first time, which possessed tumor microenvironment-respo
- Chen, Zelong,Hu, Xianjun,Jin, Ming,Pei, Yuxin,Pei, Zhichao,Pu, Liang,Wang, Yang
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supporting information
p. 10642 - 10645
(2020/10/02)
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- Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis
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Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB.
- Li, Zhihao,Bavaro, Teodora,Tengattini, Sara,Bernardini, Roberta,Mattei, Maurizio,Annunziata, Francesca,Cole, Richard B.,Zheng, Changping,Sollogoub, Matthieu,Tamborini, Lucia,Terreni, Marco,Zhang, Yongmin
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supporting information
(2020/07/27)
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- Nonenzymatic synthesis of anomerically pure, mannosylbased molecular probes for scramblase identification studies
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The chemical synthesis of molecular probes to identify and study membrane proteins involved in the biological pathway of protein glycosylation is described. Two short-chain glycolipid analogs that mimic the naturally occurring substrate mannosyl phosphoryl dolichol exhibit either photoreactive and clickable properties or allow the use of a fluorescence readout. Both probes consist of a hydrophilic mannose headgroup that is linked to a citronellol derivative via a phosphodiester bridge. Moreover, a novel phosphoramidite chemistry-based method offers a straightforward approach for the non-enzymatic incorporation of the saccharide moiety in an anomerically pure form.
- Bütikofer, Peter,H?ner, Robert,Khorev, Oleg,Langenegger, Simon M.,Menon, Anant K.,Picca, Giovanni,Probst, Markus
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supporting information
p. 1732 - 1739
(2020/09/15)
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- Preparation method of 3, 4, 6-O-triacetyl-D-glucal
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The invention relates to a preparation method of Tri-O-acetyl-D-glucal, which mainly solves the problems of volatile reagent, irritant smell, high cost and the like in the existing method. The technical scheme of the invention is as follows: the preparation method of 3, 4, 6-O-triacetyl-D-glucal comprises the following steps: peracetylated D-glucose is prepared by catalyzing D-glucose in glacial acetic acid with strong acid; the peracetylated D-glucose is brominated by a glacial acetic acid solution of hydrogen bromide to obtain brominated peracetylated D-glucose; and the brominated peracetylated D-glucose is reduced by zinc powder in an ammonium chloride solution to obtain a final product 3, 4, 6-O-triacetyl-D-glucal. The product provided by the invention has important application in thefields of glycopeptides and other polypeptide drugs.
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Paragraph 0012-0014
(2020/05/14)
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- Studies on the stereoselective synthesis and immunosuppressive activity of dihydroartemisinin-O-glycoside derivatives
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Eight new dihydroartemisinin-O-glycosides were synthesized with their relative configurations were determined based on NMR spectrum. In vitro immunosuppressive assay showed that 10α-dihydroartemisinin-β-O-D-mannoside (19a) demonstrate 88percent inhibition towards T cells proliferation and 98percent reduction in IFN-γ levels in cell media. These results suggest that dihydroartemisinin-O-glycoside as a potential lead for further in vivo evaluation.
- Bian, Hongzhu,Dong, Xun,Shen, Zhengwu,Xu, Wei,Yu, Jingfeng,Yu, Yu,Zhang, Jinghua,Zou, Xiaosu
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supporting information
(2020/07/21)
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- The effect of monosaccharides on self-assembly of benzenetricarboxamides
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The interaction between monosaccharides exhibits an important role in the assembly of monosaccharide-containing molecules. In this work, three common monosaccharides, glucose, galactose and mannose, are employed to investigate the effect of monosaccharide on the self-assembly of benzenetricarboxamide (BTA) core-containing molecules. In the presence of monosaccharides, three benzenetricarboxamide derivatives aggregate into different ordered structures. When alanine linkers are introduced to these molecules between the core and the monosacchride, morphologies of three types of monosaccharide BTAs turned to disordered, meanwhile their structures become similar with the increase of the length of alanine linkers, indicating the disappearance of the monosaccharide effects.
- Wang, Jue,Qi, Wenjing,Chen, Guosong
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supporting information
p. 587 - 591
(2019/01/04)
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- Synthesis and in vitro screening of novel heterocyclic β-D-gluco- And β-D-galactoconjugates as butyrylcholinesterase inhibitors
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The development of selective butyrylcholinesterase (BChE) inhibitors may improve the treatment of Alzheimer’s disease by increasing lower synaptic levels of the neurotransmitter acetylcholine, which is hydrolysed by acetylcholinesterase, as well as by overexpressed BChE. An increase in the synaptic levels of acetylcholine leads to normal cholinergic neurotransmission and improved cognitive functions. A series of 14 novel heterocyclic β-d-gluco- and β-d-galactoconjugates were designed and screened for inhibitory activity against BChE. In the kinetic studies, 4 out of 14 compounds showed an inhibitory effect towards BChE, with benzimidazolium and 1-benzylbenzimidazolium substituted β-d-gluco- and β-d-galacto-derivatives in a 10–50 micromolar range. The analysis performed by molecular modelling indicated key residues of the BChE active site, which contributed to a higher affinity toward the selected compounds. Sugar moiety in the inhibitor should enable better blood–brain barrier permeability, and thus increase bioavailability in the central nervous system of these compounds.
- Baumann, Kre?imir,Kordi?, Lorena,Mo?ibob, Marko,?inko, Goran,Tomi?, Sr?anka
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- Design, synthesis and molecular docking analysis of flavonoid derivatives as potential telomerase inhibitors
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Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound 5c exhibited the most potent inhibitory activity against human telomerase with an IC50 value of less than 50 μM. In vitro, the results demonstrated that compound 5c had potent anticancer activity against five classes of tumor cell lines. The molecular docking and molecular dynamics analyses binding to the human telomerase holoenzyme were performed to elucidate the binding mode of active compound 5c. This finding helps the rational design of more potent telomerase inhibitors based on the structural scaffolds of natural products.
- Cheng, Mao-Sheng,Fan, Zhan-Fang,Fu, Ya,Ho, Sai-Tim,Hu, Chun,Liu, Yang,Shaw, Pang-Chui,Wang, Jian,Wen, Rui,Zhang, Lei
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- Phosphotungstic acid as a novel acidic catalyst for carbohydrate protection and glycosylation
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This work demonstrates the utilization of phosphotungstic acid (PTA) as a novel acidic catalyst for carbohydrate reactions, such as per-O-acetylation, regioselective O-4,6 benzylidene acetal formation, regioselective O-4 ring-opening, and glycosylation. These reactions are basic and salient during the synthesis of carbohydrate-based bioactive oligomers. Phosphotungstic acid's high acidity and eco-friendly character make it a tempting alternative to corrosive homogeneous acids. The various homogenous acid catalysts were replaced by the phosphotungstic acid solely for different carbohydrate reactions. It can be widely used as a catalyst for organic reactions as it is thermally stable and easy to handle. In our work, the reactions are operated smoothly under ambient conditions; the temperature varies from 0 °C to room temperature. Good to excellent yields were obtained in all four kinds of reactions.
- Chen, Jyun-Siao,Sankar, Arumugam,Lin, Yi-Jyun,Huang, Po-Hsun,Liao, Chih-Hsiang,Wu, Shen-Shen,Wu, Hsin-Ru,Luo, Shun-Yuan
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p. 33853 - 33862
(2019/11/11)
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- Design, synthesis and bioactivity of core 1 O-glycan and its derivative on human gut microbiota
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Background: Disaccharide core 1 (Galβ1-3GalNAc) is a common O-glycan structure in nature. Biochemical studies have confirmed that the formation of the core 1 structure is an important initial step in O-glycan biosynthesis and it is of great importance for human body. Objective: Our study will provide meaningful and useful sights for O-glycan synthesis and their bioassay. And all the synthetic glycosides would be used as intermediate building blocks in the scheme developed for oligosaccharide construction. Methods: In this article, we firstly used chemical procedures to prepare core 1 and its derivative, and a novel disaccharide was efficiently synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR and MS. Then we employed three human gut symbionts belonging to Bacteroidetes, a predominantphyla in the distal gut, as models to study the bioactivity of core 1 and its derivative on human gut microbiota. Results: According to our results, both core 1 and derivative could support the growth of B. fragilis, especially the core 1 derivative, while failed to support the growth of B. thetaiotaomicron and B. ovatus. Conclusion: This suggested that the B. fragilis might have the specificity glycohydrolase to cut the glycosidic bond for acquiring monosaccharide.
- Qu, Huanhuan,Li, Baixue,Yang, Jingyi,Liang, Huaiwen,Li, Meixia,Ding, Kan
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p. 1348 - 1353
(2019/11/22)
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- Synthesis of 8-hydroxyquinoline glycoconjugates and preliminary assay of their β1,4-GalT inhibitory and anti-cancer properties
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8-Hydroxyquinoline scaffold is a privileged structure used in designing a new active agents with therapeutic potential. Its connections with the sugar unit is formed to improve the pharmacokinetic properties. The broad spectrum of activity of quinoline derivatives, especially glycoconjugates, is often associated with the ability to chelate metal ions or with the ability to intercalate into DNA. Simple and effective methods of synthesis glycoconjugates of 8-hydroxyquinoline and 8-hydroxyquinaldine derivatives, containing an O-glycosidic bond or a 1,2,3-triazole linker in their structure, have been developed. The obtained glycoconjugates were tested for their ability to inhibit β-1,4-Galactosyltransferase, as well as inhibit cancer cell proliferation. It was found that used glycoconjugation strategy influenced both improvement of activity and improvement of the bioavailability of 8-HQ derivatives. Their activity depends on type of attached sugar, presence of protecting groups in sugar moiety and presence of a linker between sugar and quinolone aglycone.
- Krawczyk, Monika,Pastuch-Gawolek, Gabriela,Mrozek-Wilczkiewicz, Anna,Kuczak, Michal,Skonieczna, Magdalena,Musiol, Robert
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p. 326 - 338
(2018/12/11)
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