Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

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

• sialic acid is deliberately mentioned [18] (see also Table 1). A more versatile set of annotation systems was built around the number of antennae. The term 3A2S denotes a triantennary N-glycan with two sialic acid residues. Obviously, this lean annotation does at first not specify linkage types and

• 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

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

• , Russian Federation 10.3762/bjoc.20.18 Abstract The development of new methods for chemical glycosylation commonly includes comparison of various glycosyl donors. An attempted comparison of chemical properties of two sialic acid-based thioglycoside glycosyl donors, differing only in the substituent at O-9

• and straightforward as it is usually considered. Keywords: concentration; glycosylation; protecting groups; reactivity; sialic acids; stereoselectivity; Introduction Glycoconjugates containing sialic acid occur on the surface of all cell types in a variety of organisms. They participate in a broad

• and conjugates are important for advancing glycobiology [12][13] and glyco-medicine [14][15]. However, the reliable installation of sialic acid residues in oligosaccharides is a rather difficult issue and poor predictability remains characteristic of the sialylation reaction [16][17][18][19][20][21

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

• Peterson de Andrade Sanaz Ahmadipour Robert A. Field Manchester Institute of Biotechnology and Department of Chemistry, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK Iceni Glycoscience Ltd, Norwich Research Park NR4 7GJ, UK 10.3762/bjoc.18.24 Abstract Sialic acid is the

• sialic acid derivatives in good yields and high purity via copper-catalysed azide–alkyne cycloaddition (CuAAC, click chemistry) and evaluated their activity towards TcTS and neuraminidase. Surprisingly, the compounds showed practically no TcTS inhibition, whereas ca. 70% inhibition was observed for

• 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

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• MECP2 regulation were all found to disproportionately regulate sialic acid and GAG synthesis pathways. Several of the TFs enriched to glycosylation pathways were either regulated by or involved in TGF-β signaling and Wnt β-catenin signaling. These TFs primarily affected glycosaminoglycan synthesis

• gangliosides. UGCG is included to consider the addition of glucose to ceramide. ST3GAL5 and ST8SIA enzymes are added to take the core ganglioside structures to the a, b, and c levels. B4GALTs and B4GALNT1 are included to account for ganglioside elongation. Decoration of the gangliosides with sialic acid occurs

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

• linear chain comprising of up to four monosaccharide units, containing glucose, galactose and N-acetylgalactosamine, to which are attached a variable number of sialic acid (N-acetylneuraminic acid) residues. The sialic acid content of the oligosaccharide, being anionic at pH 7, results in an overall

• since been rescinded [21].) To this base string are added a list of the sialic acids attached to each monosaccharide in the core, counting using the Roman numeral system, starting from the base glucose (cf. Figure 1). From the non-reducing end, write the position on the core where a sialic acid (or

• 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

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• mannose, Hex/H, 162.0528 Da), N-Acetylhexosamines (N-acetylglucosamine or N-acetylgalactosamine, HexNAc/N, 203.0794 Da), fucose (Fuc/F, 145.0579 Da), and sialic acid (N-acetylneuraminic acid, NeuAc/S, 291.0954 Da). The combinatorial possibilities of these building blocks and the variety of structural

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• α-2,6-linked sialic acid (NNa6) whose linkage position is unknown. Here, the “ | ” is used to separate the fragment(s) and core structure components (UR6). In the interest of demonstrating the reach of single letter LC monosaccharides (Table 4), we provide a monosaccharide network suggesting

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• virus uses the haemagglutinin glycoprotein to recognise and bind sialic acid decorations of human cells in the respiratory tract [7]. Glycosylation is also used by pathogens to evade the host’s immune system via glycan shields [8][9][10], and thereby to delay an immune response [11]. The structural

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

• . Thus, the drift strains (#1–10) cluster together in the red cluster, in comparison to the New York H3N2 strain in green, all of which are separated from the purple cluster of the H1N1 strains. (B) To visualize specific binding to lactosamine (Galb1-4GalNAc) in the absence of sialic acid, the dataset is

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• interesting observations can be concluded from the quantitation including: a) core fucose sialic acid based glycans had increased abundances in bioreactor condition b7, b8, and b9, b) mannosylation was increased in b7 and b9, c) neutral fucosylation decreased for b7 and b9. However, FA1 did not follow this

• . Database matched glycans are shown in Oxford linear notation [19]. The CE APTS database hits are marked with a circle and a corresponding error bar showing the GU tolerance. All glycans with core fucose were α-1→6 linkage, galactose were β-1→4 linkage and all sialic acid linkages were α-2→3 linkage. All

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

• University, Hsinchu 300, Taiwan 10.3762/bjoc.15.295 Abstract Sialic acid-containing glycans are found in different sialic acid forms and a variety of glycosidic linkages in biologically active glycoconjugates. Hence, the preparation of suitably protected sialyl building blocks requires high attention in

• ]. 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

• gangliosides and other Neu5Ac-containing glycans after its 2,7-anhydro backbone has been opened. Representative structures of bacterial glycans containing sialic acid, which can be chemically synthesized from sialyl donors, are illustrated in Figure 1 [2][3][4][5][22][23][24]. One way to obtain Neu5Ac

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

• , distinct cell-surface staining after MGE. We further found that the amide-linked Cp-modified glucosamine derivative but not the Cyoc-modified glucosamine is metabolically converted to the corresponding sialic acid. Keywords: bioorthogonal chemistry; carbohydrates; cyclopropenes; inverse electron-demand

• is much more efficiently metabolized and converted to the corresponding sialic acid than Ac4ManNCyoc. Determination of incorporation efficiencies To confirm the hypothesis of different metabolization efficiencies of the mannosamine derivatives, we intended to quantify the proportion of cellular

• ) [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

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

• -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

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• arylglycosylation was also extended for the synthesis of aureolic acid antibiotics [21][51][52]. In search of convenient methods for the synthesis of aryl sialosides, Gao et al. explored the scope of the Mitsunobu reaction with the sialic acid derivative 49, employing a range of phenols 50–58 in acetonitrile to

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

• branched pentasaccharide [Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-Glcβ1-1-ceramide] bearing a ceramide moiety at the anomeric center of the Glc moiety (Figure 2). The terminal galactose residue of GM1 is buried most deeply inside the cavity of CTB [12][14], while the sialic acid branch sits in a wider shallow

• affinity of these inhibitors was measured using weak affinity chromatography and some molecules displayed enhancement of affinity over the individual epitome ‘Galactose’ [35]. One such compound 3 has found to co-crystallise with CTB in a way that the galactose and sialic acid groups bind to adjacent CTB

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• degradation. The original procedure [82] for the isolation of SGP first involved deproteinization by treatment with 90% phenol and washing with Et2O, and then repeated purification by size exclusion chromatography (SEC, Sephadex G-50, followed by Sephadex G-25) from which sialic acid positive fractions were

• (2-chloro-1,3-dimethyl-1H-benzimidazol-3-ium chloride, CDMBI) has also been reported to be efficient at this transformation [91]. Furthermore removal of the terminal sialic acid residues of the free oligosaccharide by treatment with a neuraminidase allows the production of truncated complex

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• had been deposited on a carbon electrode with an azide-terminated sialic acid derivative [74]. Firstly, AuNPs were electro-deposited on a carbon electrode. Then a solution of an alkyne-terminated disulphide (4,7,10,13,38,41,44,47-octaoxa-25,26-dithiapentaconta-1,49-diyne) was ‘dropped over’ the AuNP

• -electrode system to cover the AuNP surfaces with alkyne-terminated SAMs (Scheme 10). Next, a CuAAC reaction was used to couple the alkyne-functionalized AuNPs to an azide-linked sialic acid derivative, to produce GAuNPs attached to the carbon electrode. This sialic acid-functionalized GAuNP-carbon electrode

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• scattering. Moreover, a selective detection of the influenza virus can be accomplished. Viral hemagglutinin (HA) protein, in fact, can bind selectively sialic acid residues, but the human influenza virus recognizes the sialic acid α(2,6)galactose sequence while the avian virus recognizes sialic acid α(2,3

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• Galanthusnivalis agglutinin (GNA, digoxigenin-conjugated lectin) (Figure 1F), indicating the predominance of the paucimannose structure in insect cells. In contrast, mammalian N-glycans have terminal sialic acid residues with more antennal diversity. The band at approximately 250 kDa corresponds to an oligomeric

• peptides from primary sequence databases with Mascot (http://www.matrixscience.com/). The biological function of recombinant proteins of mammalian origin expressed in insect cells may be altered by different N-glycan status. We observed that the terminal sialic acid residues are essential for the GABA

Influence of length and flexibility of spacers on the binding affinity of divalent ligands

• Susanne Liese and
• Roland R. Netz

Beilstein J. Org. Chem. 2015, 11, 804–816, doi:10.3762/bjoc.11.90

• Equation 16 for a stiff spacer) is substituted into Equation 48: As an example that is relevant for medical applications we want to briefly discuss the interaction between hemagglutinin (HA), a receptor protein on the surface of influenza viruses, and its ligand sialic acid (SA). The dissociation constant

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

• 10.3762/bjoc.11.69 Abstract A sialic acid glycosyl phosphate building block was designed and synthesized. This building block was used to prepare α-sialylated oligosaccharides by automated solid-phase synthesis selectively. Keywords: α-sialylation; automated synthesis; glycosylation; sialic acid; solid

• -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

• incorporation of sialic acid–galactose disaccharide building blocks [5][11]. Here, we describe a sialic acid building block that can be utilized for automated glycan assembly. Results and Discussion Sialylating oligosaccharides in high yield and α-selectivity was challenging since the presence of a C-1 carboxyl

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• virus to the host cell proved to be potent drug candidates [4][5][6][7][8][9]. Those inhibitors bind to the virus envelope spike protein hemagglutinin (HA) which is organized as a homotrimer. In particular, inhibitors competing for the highly conserved binding site for sialic acid, which is the natural

• not been elucidated in detail. Matsubara et al. introduced a sugar mimetic peptide, which binds to the sialic acid binding pocket of HA [13]. In order to increase the inhibitory capacity of the peptide, a stearyl group has been attached to the mimetic peptide, presumably leading to the formation of a

• study, stearylated PeBGF (C18-PeBGF) has been compared with EB, the stearylated sialic acid mimetic (C18-s2s), and the stearylated control peptide with the reverse amino acid sequence (C18-rs2s) in respect to their potential to inhibit virus mediated hemagglutination, and to lyse red blood cells

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp

• terminal units and it has been demonstrated that it plays an important role in the infection. Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. The transfer reaction of sialic acid was performed using a recombinant TcTS and 3

• ’-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• are small enough to be accepted by cellular enzymes during MOE [22][23][24]. Also, they are stable in aqueous solution in the presence of biological nucleophiles [22][28]. Consequently, cyclopropene tags were attached by an amide linkage to sialic acid [22] and ManNAc derivatives including Ac4ManNCyc

• (4) [23] (Figure 1) to label sialic acid residues on the surface of living cells via MOE. Since carbamate-linked methylcyclopropenes have significantly higher reaction rates in DAinv reactions with tetrazines [22][28], we recently introduced Ac4ManNCyoc (3) as a derivative for rapid labeling of

• -azidoacetylmannosamine (ManNAz) and subsequently to the corresponding sialic acid [32][33] following a metabolic pathway known also for the natural sugars [34]. Also, the efficiency by which non-natural GlcNAc and GalNAc derivatives are metabolized is dependent on the type of modification and the cell line. These