100678-43-1Relevant articles and documents
Synthesis of γ-lactone-type sialic acid, an isomer of 2,3-dehydrosialic acid
Sawada, Yoshiharu,Nakatsuka, Shin-Ichi
, p. 1106 - 1107 (2010)
An efficient synthesis of γ-lactone-type sialic acid, which is an isomer of 2,3-dehydrosialic acid, was achieved from the corresponding sialic ester. The sialic ester was reconstructed from the γ-lactone in a 95% yield. The γ-lactone structure was determined by methylating to its corresponding methyl ether.
Glycoprotein labeling with click chemistry (GLCC) and carbohydrate detection
Wu, Zhengliang L.,Huang, Xinyi,Burton, Andrew J.,Swift, Karl A.D.
, p. 1 - 6 (2015)
Molecular labeling and detection techniques are essential to research in life science. Here, a method for glycoprotein labeling/carbohydrate detection through glycan replacement, termed glycoprotein labeling with click chemistry (GLCC), is described. In this method, a glycoprotein is first treated with specific glycosidases to remove certain sugar residues, a procedure that creates acceptor sites for a specific glycosyltransferase. A 'clickable' monosaccharide is then installed onto these sites by the glycosyltransferase. This modified glycoprotein is then conjugated to a reporter molecule using a click chemistry reaction. For glycoproteins that already contain vacant glycosylation sites, deglycosylation is not needed before the labeling step. As a demonstration, labeling on fetal bovine fetuin, mouse immunoglobulin IgG and bacterial expressed human TNFα and TNFβ are shown. Compared to traditional ways of protein labeling, labeling at glycosylation sites with GLCC is considerably more specific and less likely to have adverse effects, and, when utilized as a method for carbohydrate detection, this method is also highly specific and sensitive.
Synthesis of highly controlled carbohydrate-polymer based hybrid structures by combining heparin fragments and sialic acid derivatives, and solid phase polymer synthesis
Baier, Mischa,Ruppertz, Jana L.,Pfleiderer, Moritz M.,Blaum, B?rbel S.,Hartmann, Laura
, p. 10487 - 10490 (2018)
Heparin is a polymeric carbohydrate with a variety of biomedical applications that is particularly challenging from a synthetic point of view. Here, we present the synthesis of carbohydrate-polymer based hybrid structures by combining defined heparin fragments with monodisperse, sequence-controlled glycooligo(amidoamines) suitable as glycan mimetic model compounds of heparin as demonstrated by STD-NMR binding studies with viral capsids.
Synthesis of a New Series of Sialylated Homo- and Heterovalent Glycoclusters by using Orthogonal Ligations
Daskhan, Gour Chand,Pifferi, Carlo,Renaudet, Olivier
, p. 477 - 484 (2016)
The synthesis of heteroglycoclusters (hGCs) is being subjected to rising interest, owing to their potential applications in glycobiology. In this paper, we report an efficient and straightforward convergent protocol based on orthogonal chemoselective ligations to prepare structurally well-defined cyclopeptide-based homo- and heterovalent glycoconjugates displaying 5-N-acetyl-neuraminic acid (Neu5Ac), galactose (Gal), and/or N-acetyl glucosamine (GlcNAc). We first used copper-catalyzed azide–alkyne cycloaddition and/or thiol-ene coupling to conjugate propargylated α-sialic acid 3, β-GlcNAc thiol 5, and β-Gal thiol 6 onto cyclopeptide scaffolds 7–9 to prepare tetravalent homoglycoclusters (10–12) and hGCs (13–14) with 2:2 combinations of sugars. In addition, we have demonstrated that 1,2-diethoxycyclobutene-3,4-dione can be used as a bivalent linker to prepare various octavalent hGCs (16, 19, and 20) in a controlled manner from these tetravalent structures.
Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance
Heise, Torben,Langereis, Jeroen D.,Rossing, Emiel,de Jonge, Marien I.,Adema, Gosse J.,Büll, Christian,Boltje, Thomas J.
, p. 1279 - 8,1285 (2018)
Pathogens such as non-typeable Haemophilus influenzae (NTHi) evade the immune system by presenting host-derived sialic acids. NTHi cannot synthesize sialic acids and therefore needs to utilize sialic acids originating from host tissue. Here we report sialic acid-based probes to visualize and inhibit the transfer of host sialic acids to NTHi. Inhibition of sialic acid utilization by NTHi enhanced serum-mediated killing. Furthermore, in an in vitro model of the human respiratory tract, we demonstrate efficient inhibition of sialic acid transfer from primary human bronchial epithelial cells to NTHi using bioorthogonal chemistry. Molecular mimicry of non-typeable Haemophilus influenzae (NTHi) with host sialic acid sugars mediates resistance to serum killing and increases virulence. Heise et al. have developed sialic acid derivatives that allow either visualization or inhibition of host sialic acid transfer to NTHi, the latter enhancing serum-mediated killing.
Glycopeptide nanofiber platform for Aβ-sialic acid interaction analysis and highly sensitive detection of Aβ
Lei, Li,Geng, Rui,Xu, Zhiai,Dang, Yijing,Hu, Xianli,Li, Lingling,Geng, Ping,Tian, Yang,Zhang, Wen
, p. 8129 - 8136 (2019)
The variation of amyloid β peptide (Aβ) concentration and Aβ aggregation are closely associated with the etiology of Alzheimer’s diseases (AD). The interaction of Aβ with the monosialoganglioside-rich neuronal cell membrane has been suggested to influence Aβ aggregation. Therefore, studies on the mechanism of Aβ and sialic acids (SA) interaction would greatly contribute to better understanding the pathogenesis of AD. Herein, we report a novel approach for Aβ?SA interaction analysis and highly sensitive Aβ detection by mimicing the cell surface presentation of SA clusters through engineering of SA-modified peptide nanofiber (SANF). The SANF displayed well-ordered 1D nanostructure with high density of SA on surface. Using FAM-labeled Aβ fragments of Aβ1?16, Aβ16?23, and Aβ24?40, the interaction between Aβ and SA was evaluated by the fluorescence titration experiments. It was found that the order of the SA-binding affinity was Aβ1?16 > Aβ24?40 > Aβ16?23. Importantly, the presence of full-length Aβ1?40 monomer triggered a significant fluorescence enhancement due to the multivalent binding of Aβ1?40 to the nanofiber. This fluorescent turn-on response showed high selectivity and sensitivity for Aβ1?40 detection and the method was further used for Aβ aggregation process monitoring and inhibitor screening. The results suggest the proposed strategy is promising to serve as a tool for mechanism study and the early diagnosis of Alzheimer’s disease.
Enzymes in Carbohydrate Synthesis: N-Acetylneuraminic Acid Aldolase Catalyzed Reactions and Preparation of N-Acetyl-2-deoxy-D-neuraminic Acid Derivatives
Kim, Mahn-Joo,Hennen, William J.,Sweers, H. Marcel,Wong, Chi-Huey
, p. 6481 - 6486 (1988)
This paper describes the structural characteristics of substrates accepted by N-acetylneuraminic acid (Neu5Ac) aldolase (E.C.4.1.3.3), the results from its stability studies, its use in the synthesis of Neu5Ac and 9-O-acetyl-Neu5Ac (Neu5,9Ac2), and the chemical conversion of Neu5Ac to the 2-deoxy derivatives.Values of kinetic parameters (Km and Vmax) for 14 aldoses including N-acetyl-D-mannosamine (ManNAc) and pyruvate were determined at pH 7.5 and 25 deg C in the direction of condensation.The 30-50-mmol-scale synthesis using ManNAc, excess pyruvate, and PAN-immobilized Neu5Ac aldolase provided multigram quantities of Neu5Ac (yield, 87-91 percent in solution and 67 percent in isolated products) without a significant loss of enzyme activity.The synthesis using two separate enzyme reactions, acetylation of ManNAc to 6-O-acetylManNAc catalyzed by protease N and condensation of 6-O-acetylManNAc with pyruvate catalyzed by Neu5Ac aldolase, provided Neu5,9Ac2 in 59 percent overall yield.To illustrate the utility of Neu5Ac as a synthetic starting material, a potential inhibitor of Neu5Ac-associated enzymes was prepared.Three chemical steps from Neu5Ac provided methyl 4,7,8,9-tetra-O-acetyl-N-acetyl-2-deoxy-α-neuraminic acid (2-deoxy-α-Neu4,5,7,8,9Ac5OMe) in 50 percent overall yield.Its structure was analyzed by 1H and 13C NMR spectroscopy and X-ray crystallography.
Anti-influenza virus activity of biflavonoids
Miki, Kazuhiko,Nagai, Takayuki,Suzuki, Kazushige,Tsujimura, Ryo,Koyama, Kiyotaka,Kinoshita, Kaoru,Furuhata, Kimio,Yamada, Haruki,Takahashi, Kunio
, p. 772 - 775 (2007)
Ginkgetin was found to inhibit the influenza virus sialidase. Ginkgetin-sialic acid conjugates showed a significant survival effect in the influenza-virus-infected mice.
Design, synthesis and biological activity evaluation of novel conjugated sialic acid and pentacyclic triterpene derivatives as anti-influenza entry inhibitors
Han, Xu,Shi, Yongying,Si, Longlong,Fan, Zibo,Wang, Han,Xu, Renyang,Jiao, Pingxuan,Meng, Kun,Tian, Zhenyu,Zhou, Xiaoshu,Jin, Hongwei,Wu, Xinyu,Chen, Hong,Zhang, Yongmin,Zhang, Lihe,Xiao, Sulong,Zhou, Demin
, p. 1932 - 1945 (2016)
Influenza virus is a major human pathogen that causes annual epidemics and occasional pandemics. Recently, plant-derived pentacyclic triterpenes have been shown to act as highly potent anti-viral agents by efficiently preventing the attachment of the virion to the host cells. In this report, we conjugated sialic acid with oleanolic acid (OA), a natural product with broad antiviral entry activity, as well as three other analogs echinocystic acid (EA), ursolic acid (UA) and betulinic acid (BA). A total of 24 conjugated sialic acid and pentacyclic triterpene derivatives with different linkers were synthesized and evaluated for antiviral activity against influenza A/WSN/33 (H1N1) virus in MDCK cell culture. The most potent compound had an IC50 of 41.2 μM. Time-of-addition, hemagglutination inhibition (HI), surface plasmon resonance (SPR) and molecular docking assays demonstrated that compound 20a acted as an influenza virus entry inhibitor by preventing the binding of influenza virus hemagglutinin (HA) protein to host cells.
Synthesis of O-Glycolyl-Linked Neuraminic Acids through a Spirocyclic Intermediate
McAuliffe, Joseph C.,Rabuka, David,Hindsgaul, Ole
, p. 3067 - 3069 (2002)
(Equation Presented) The neuraminic acid derivative 5 is readily converted in several steps to the neuraminic acid dimer 12, linked through the hydroxyl of a 5-N-glycolyl group in an α-2,5 glycosidic linkage. The sequence is shown to proceed through a spi
