Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• residues. Following the example of alpha-Gal residues, we can write a Neu5Ac(α2-6)Gal(β1-4)GlcNAc(β1-2) antenna as Na6-4 while retaining the complete structural information (Figure 3). Rarely, a sialic acid residue is linked directly to GlcNAc as in bovine fetuin [42]. As this element was found on

• found in β1-4 linkage. Neu5Ac has no other choice than the 3-position. The two residues are linked to a galactose, hence a hyphen and the pertinent linkage (Figure 9). The letter A itself is hidden as in sialylated antennae (Figure 3). Finally, a hypothetical N-glycan shall exemplify the annotation of

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• anomeric ratio values (α/β, see Figure 2 and Table S1 in Supporting Information File 1). For determination of the α/β ratio, integral intensities of signals of α-H-3eq and β-H-3eq of Neu5Ac residue of 4 were used (for relevant parts of the 1H NMR spectra see Figures S1–S4 in Supporting Information File 1

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• reasons, the synthesis of N-acetylneuraminic acid (Neu5Ac) in a continuous fixed-bed reactor by an immobilized epimerase and aldolase was investigated in detail. The immobilized enzymes showed high stability, with half-life times > 173 days under storage conditions (6 °C in buffer) and reusability over 50

• the position of the reaction equilibrium. By this, equilibrium conversion, selectivity, and yield were increased from 57.9% to 63.9%, 81.9% to 84.7%, and 47.5% to 54.1%, respectively. This indicates a reduction in molar volume from N-acetyl-ᴅ-glucosamine (GlcNAc) and pyruvate (Pyr) to Neu5Ac. In

• for the aldolase from 108 to 42 mM and 91 to 37 mM, respectively. Keywords: aldolase; continuous fixed-bed reactor; enzyme; epimerase; GlcNAc; high pressure; immobilization; ManNAc; Neu5Ac; pyruvate; Introduction In times of a pandemic, the importance of substances to enhance the human immune system

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• differences in sialidases that need to be addressed in order to achieve selective inhibition. Keywords: inhibition; neuraminidase; sialic acid; trans-sialidase; 1,2,3-triazole; Introduction Amongst the diversity of glycans present in living organisms, N-acetylneuraminic acid (Neu5Ac, sialic acid) is

• pentaerythritol homoglycocluster reported by the Carvalho group [17] and a C-sialoside bearing phenylpropyl group at C-2 [18] (Figure 1C). In the context of mimicking the terminal sugars α-ᴅ-Neu5Ac(2,3)-β-ᴅ-Gal of Trypanosoma cruzi mucins to obtain potent TcTS inhibitors, our group previously synthesised a small

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• the context. In this work, we consider only four monosaccharides and their corresponding letters: Glc (G), Gal (L), Neu5Ac (S) and GalNAc (V). In IUPAC form (see Table 1), we can write the carbohydrate portion of the ganglioside GM1a (Figure 1) as any of the following: Galb1-3GalNAcb1-4[Neu5Aca2-3

• ]Galb1-4GlcCer (IUPAC) Lb3Vb4[Sa3]Lb4GbT (Glycologue, full) L3Vb4[S3]L4GT (Glycologue, abbreviated) Glycologue makes the further assumption that each sugar as it appears in the acceptor has a default anomer, with Glc and Gal being β, and Neu5Ac and GalNAc being α, which allows the a and b notation to be

• sialic acid chain) appears, as the uppercase Roman numeral, superscripting the linkage position after as the Arabic numeral, followed by “Neu5Ac”; if a chain of sialic acids is present, place the “Neu5Ac” in parentheses and subscript the number of residues after, e.g., IV3(Neu5Ac)2. Repeat this procedure

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• filtered for lactosamine containing glycan data and data for glycans with Neu5Ac are eliminated from the pool. A Bubble Plot of this filtered data shows clearly that the drift strains (#1–10) bind better to the lactosamine containing glycans without Neu5Ac as compared to the New York H3N2 strain and the

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• ]. N-Acetylneuraminic acid (Neu5Ac) is the most studied monosaccharide from the 50 derivatives of sialic acid that are found in nature. The most common glycosidic linkages of Neu5Ac in glycoconjugates are α(2→3) and α(2→6) to galactose, α(2→8) and α(2→9) in polysialic acids [2][3], fucosyl and

• galactosyl α(1→4) to Neu5Ac, and intramolecularly C-7-to-C-2-linked (via oxygen), forming 2,7-anhydro-Neu5Ac [4][5][6]. Owing to the substantial role of sialic acids in biological systems, numerous synthetic methods have been described in the literature [7][8][9][10][11][12][13][14][15][16]. 2,7-Anhydro

• -Neu5Ac is the main prebiotic, which is utilized as a sole carbon source for human gut commensal anaerobic bacterium and plays a key biological role in body fluids and secretion [17][18][19]. Upon cleaving the internal ketal ring and protection of the OH-4 group, further modifications at carbon C-7 and

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• ) [29][30][31]. As described earlier [20], DMB selectively reacts with α-keto acids such as N-acetylneuraminic acid (Neu5Ac), the most abundant natural sialic acid in human cells [1], forming a fluorophore. Analysis by RP-HPLC equipped with a fluorescence detector allows the detection of natural and

• modified sialic acids. The incorporation efficiency IE can be calculated from the integrals I of the RP-HPLC signals of DMB-labeled Neu5Ac (INeu5Ac) and the respective DMB-labeled modified sialic acid (INeu5R) according to the formula IE = INeu5R (INeu5R + INeu5Ac)−1 100%. Unfortunately, it turned out that

• labeling gave reference compound DMB-Neu5Cyoc(H2) that was analyzed by RP-HPLC-MS (Figure S4, Supporting Information File 1). Additionally, we synthesized the literature known DMB derivatives of the natural sialic acid Neu5Ac [29] and of sodium pyruvate [30] as reference compounds to determine their

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• -D-muramic acid; Neu5Ac: N-acetyl-D-neuraminic acid; PG: peptidoglycan; L-Rhap: L-rhamnopyranosides; sMTL: secreted 13 kDa large lectin from Mtb; TB: tuberculosis; TDM: trehalose 6,6'-dimycolate; TMM: trehalose 6-monomycolate; T4P: type IV pili. Immune cells (e.g., macrophages) and epithelial cells

• -GalNAc), and sialic acid residues, such as N-acetyl-D-neuraminic acid (Neu5Ac). While most of the internal glycosides in eukaryotic oligosaccharides are β-linked, terminally localized carbohydrates are often attached via an α-glycosidic bond. (R = H or glycosidic linkage; the figure of the Mtb cell wall

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• -tetrasaccharide 1 was made in which the recognition units, the terminal galactose and Neu5Ac, were attached onto the DCCHD scaffold. Inhibition assays of the oligosaccharide mimetic with CT and LT showed similar potency as that of natural ligands [32]. But, the alpha-sialylation was the bottleneck step in the

• synthesis, so they designed second generation inhibitors by changing the synthetically challenging α-Neu5Ac with alpha-hydroxy acids 2 [33][34]. Using a combinatorial approach, a library of non-hydrolyzable, non O-glycosidic third generation inhibitors were synthesised using appropriate linkers. The CTB

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• -phase synthesis; Introduction N-Acetylneuraminic acid (sialic acid, Neu5Ac) is an important component of mammalian glycans and key to many recognition events of biomedical relevance including cell–cell recognition, signaling, and the immune response [1]. Sialic acids are present in tumor-associated

• carbohydrate antigens (TACAs) such as the sialyl-Tn antigen (sTn) [2]. Neu5Ac is often the terminal residue and is usually linked via an α-(2,3) or α-(2,6) linkage to galactose (Gal) (Figure 1) [3]. Automated glycan assembly enables rapid access to structurally defined oligosaccharides [4][5] including

• synthesis in the future as well. The tumor associated sTn carbohydrate antigen (Neu5Ac-α(2,6)GalNAc-α(1,1)linker) disaccharide 17, that resembles the sTn antigen glycan framework (Neu5Ac-α(2,6)GalNAc-α(1,1)Ser/Thr) was synthesized. In order to install the cis-glycoside formed by the union of the

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• -linked N-acetylglucosamine or α-linked Neu5Ac, 3,4-O-isopropylidene protection of α-linked azido-propyl N-acetyl galactosamine derivative 18 [22] was carried out in DMF using p-TsOH and 2,2-dimethoxypropane to afford glycosyl acceptor 19 in 77% yield as the only regioisomer ready for glycosylation. To

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• found in this data set [66]. However, different anomeric configurations and some substitutions, such as sulfate groups, were ignored, and no distinction was made between N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). The large number of different oligosaccharides that are

Preparation of aminoethyl glycosides for glycoconjugation

• Robert Šardzík,
• Gavin T. Noble,
• Martin J. Weissenborn,
• Andrew Martin,
• Simon J. Webb and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2010, 6, 699–703, doi:10.3762/bjoc.6.81

• procedures involving sialic acid are generally challenging. In our hands activation as the chloride (prepared from Neu5Ac in 3 steps) using silver carbonate (Method F) gave reasonable yields of 19. Deprotection reactions The general deprotection for compounds 10–18 is shown in Scheme 2. Acetates were cleaved

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• glycan structures of various types forming the individual, dynamic glycocalyx of each cell type. These glycolipids and glycoproteins often carry sialic acids, in humans N-acetylneuraminic acid (Neu5Ac, 1, Scheme 1), at their terminal position which mediate cell-cell recognition and signal transduction

• analogues enter the cell by pinocytosis and are incorporated into the cellular glycosylation machinery by active transporter systems [5]. In other mammals N-glycolylneuraminic acid (Neu5Gc, 2, Scheme 1) corresponds to Neu5Ac 1 found in humans. Although the human gene for the synthesis of Neu5Gc 2 is

• the previously described pinocytosis processes (Scheme 4) or by an, as yet, unknown internalization mechanism [5]. It is believed that Neu5Hex enters the nucleus and enhances the genetic feedback control of the GNE coding gene which blocks the synthesis of natural Neu5Ac [11][13]. Alkyne- or azide