Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• . Additionally, numerous other steps involving protecting group removal and installation are required to assure regio- and stereoselective glycan assembly. One-pot strategies for oligosaccharide synthesis can streamline the process by sequential iterative glycosylations, without the need for work-up and

• and reducing end functionality. Results and Discussion As part of a project on the synthesis of glycan fragments derived from arabinogalactan proteins (AGPs) [17][18], we sought to prepare a β1→6 linked galactan as a chemical probe. We elected to prepare the galactan with a pyrene-containing aglycone

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• be enhanced by increasing the number of glycan antigens incorporated onto the carrier protein. The utilization of other conjugation chemistries enabling the achievement of higher carbohydrate loadings and the study of the effect of different glycan–protein ratios on glycoconjugates prepared from

• these short synthetic MenX fragments also deserve further exploration. Experimental General procedure for conjugation of fragments 1–3. This procedure is similar to that reported in reference [27]. The glycan (10 μmol) dissolved in DMSO (250 μL) containing triethylamine (25 equiv), was slowly dropped

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

• ; metabolic oligosaccharide engineering; Introduction The glycan chains of glycoproteins and lipids have been shown to be involved in numerous biological recognition and regulation events [1]. Glycan research, especially the visualization of glycoconjugates in vitro and in vivo, has significantly profited

• bioorthogonal labeling reactions that allow visualization [5][6]. Whereas in the first report on glycan labeling by this approach the ketone–hydrazide ligation was employed [7], later investigations mainly relied on the Staudinger ligation [8] and azide–alkyne [3 + 2] cycloaddition (copper-catalyzed [9][10] or

• -GlcNAcylated proteins). Subsequently, a ligation reaction is performed to visualize the glycan. Synthesis of the cyclopropene-modified hexosamine derivatives 1 and 2. Labeling strategy for metabolically incorporated monosaccharides. Supporting Information Additional MOE experiments and 1H and 13C NMR spectra

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• a series of carbohydrate-based ligands to galectin-3, which binds to lactose significantly better than to galactose or to N-acetylgalactosamine but does not bind to mannose [22][23][24]. Both the glycan ligand and the topological display on the cell surface are required for high affinity, selective

• binding of galectins, as demonstrated in galectin binding studies with neuroblastoma cells [25]. Here, we demonstrate that glycodendrimers bearing lactose can be used to form large, discrete aggregates of galectin-3. Since, as noted above, glycan clustering and galectin-3-mediated aggregations have been

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• yielding a more defined product. Thus, glycoPEGylation was successfully applied to the introduction of a PEGylated sialic acid to a preexisting or enzymatically linked glycan in a protein. Carbohydrates are now recognized as playing an important role in host–pathogen interactions in protozoal, bacterial

• steric effects [31]. The strategy is based on the finding that certain PEGylated nucleotide-sugars are effectively transferred to a glycan acceptor by the corresponding glycosyltransferase. A modified sialic acid PEGylated at the 5’-amino position in the CMP nucleotide (CMP-SA-5-NHCOCH2NHPEG) can be

• transferred to a glycan acceptor in a glycoprotein by a sialyltransferase [32][33]. A chemoenzymatic method for its preparation is shown in Scheme 1. It is based on the coupling of Fmoc-glycyl-mannosamine with pyruvate catalized by SA-aldolase to afford the N-protected sialic acid. After reaction with CTP

Biantennary oligoglycines and glyco-oligoglycines self-associating in aqueous medium

• Svetlana V. Tsygankova,
• Alexander A. Chinarev,
• Alexander B. Tuzikov,
• Nikolai Severin,
• Alexey A. Kalachev,
• Juergen P. Rabe,
• Alexandra S. Gambaryan and
• Nicolai V. Bovin

Beilstein J. Org. Chem. 2014, 10, 1372–1382, doi:10.3762/bjoc.10.140

• an antiviral activity three orders of magnitude higher than the activity of non-associating analogs [2]. Similar triantennary molecules with sialo-glycan located in the molecule “head”, however, appear to display a low activity [16]. Thus, it was interesting to study the antiviral activity of sialo

• derivatives of biantennary oligoglycines in relation to their propensity to associate in aqueous solutions. The fact that a sialylated biantennary peptide is capable of association in an aqueous solution similarly to glycan-free peptides is confirmed by DLC data. The average size of the sialoglycopeptide

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• carbohydrate derived α,β-unsaturated ester [47][48][49][50]. In the present article, a new class of C-linked β-glycopeptide scaffolds 1–8 (Figure 2) were synthesized and investigated with respect to secondary structures, along with the influence of glycan modifications on peptide conformation [24][25], and 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

• -galactopyranose monosaccharide and the side-chain hydroxy groups. Herein we report a convergent approach for the highly efficient synthesis of mucin type O-glycan fragments 1–7 (Figure 1) containing an α-linked 3-aminopropyl-spacer ready for covalent attachment to glycoarray platforms. Results and Discussion A

• followed by reduction of the azide group in the linker by catalytic hydrogenolysis using hydrogen and Pd/C to give trisaccharide 7 in 52% yield, after the 5 step unmasking sequence. Conclusion A highly convergent and stereoselective strategy has been used to access mucin-type glycan targets 1–7. The

• compounds 1–7 were produced functionalized with an amine linker ready to be incorporated onto glycoarray platforms for high throughput biological screening [31]. Structure of mucin-type oligosaccharide fragments synthesized. Synthesis of glycan targets 2–4. Synthesis of disaccharide targets 5 and 6

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• accomplished by amidation with an azido-amine linker followed by Cu(I)-catalyzed azide–alkyne cycloaddition with propargyl sugars. Subsequent Teoc deprotection and conjugation with pyrenyl isothiocyanates afforded well-defined end-labeled glycopolymers. Keywords: capping agent; carbohydrate; glycan; olefin

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• -Garner aldehydes. These differentially protected monosaccharide building blocks were utilized to prepare disaccharides present on the surface of Pseudomonas aeruginosa bacteria. Keywords: de novo synthesis; fucosamine; glycan; pseudomonas aeruginosa; vaccine; Introduction Protein functions are directly

• (four steps, two chromatographic purifications) that after the direct oxidation–dihydroxylation–peracetylation protocol yielded the desired L-fucosamine building block L-8a (Scheme 5). Synthesis of fucosamine-containing disaccharides To facilitate the use of the bacterial monosaccharides in the glycan

• -linked glycan (Figure 1). Conclusion The de novo synthesis of differentially protected D- and L-fucosamine building blocks from D- and L-Garner aldehyde is reported. Placement of a naphthyl ether protecting group at the C3 position allows for further elongation by glycosylation. The key oxidation step

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

• of the N-glycosides 8–10 (Scheme 3) mediated with ammonia in aqueous methanolic solution led to de-O-acetylation of the glycan moieties along with aminolysis of the oxadiazole ring affording 2-N-(glycosyl)thiosemicarbazides 11–13 instead of the corresponding nucleosides 14–16. The oxadiazole ring

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• issues. Cleavage of the linker by hydrogenolysis results in a free amine functionality for the immobilization of oligosaccharides on glycan arrays or for the synthesis of glycoconjugates. Hydrogenolysis on a solid support has been used previously in peptide chemistry [37]. In the early 1980s, catalytic

• linker 1. Cleavage by hydrogenolysis from a solid support reveals a conjugation site for the synthesis of glycoconjugates or glycan arrays and simultaneously removes permanent benzyl protecting groups. The linker can be coupled to amino- and chloro-functionalized resins. By placement of insert 2 on amino

Synthesis of a derivative of α-D-Glcp(1->2)-D-Galf suitable for further glycosylation and of α-D-Glcp(1->2)-D-Gal, a disaccharide fragment obtained from varianose

• Carla Marino,
• Carlos Lima,
• Karina Mariño and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2012, 8, 2142–2148, doi:10.3762/bjoc.8.241

• ; glucosylgalactofuranose; glycosylaldonolactone; Penicillium varians; varianose; Introduction Carbohydrates are involved in a wide range of biological processes; they play important roles in host–pathogen interactions and in the immune response, where protein–glycan interactions mediate a variety of biological processes

• , including cell trafficking, activation, differentiation and survival [1][2]. The variety and distinctive chemical properties of carbohydrates make them ideal units of condensed information, as variability is achieved not only in the glycan sequence but also in their spatial distribution. As a result

• , establishing the connection between the glycan structure and its biological function, a discipline called functional glycomics, is one of the most challenging areas nowadays and requires a broad interdisciplinary approach. Penicillium varians elaborates an unusual polysaccharide called varianose [3] that

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• revealed during final deprotection serves in the formation of glycoconjugates and glycan microarrays [19]. Synthesis of 10 relied on key intermediates 4 and 6 (Scheme 1). Monobenzylated amine 4 was prepared by reductive amination [20]. An established three-step synthesis starting with hydrocinnamic acid

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• the solid-phase synthesis of sialosides we undertook a model solution-phase synthesis of the glycan portion of GM3 ganglioside 16 (Scheme 2). GM3 serves as an important receptor for viral infection [24][25] and contains the common sialyl α-(2→3) galactose motif. The key step en route to compound 16

• were applied to the synthesis of GM3 trisaccharide 16 previously prepared in solution phase (see above). Glucose thioglycoside building block 21 and disaccharide building block 4 served for the assembly of 16 (Scheme 4). Final saponification afforded the partially protected glycan 22 in 40% overall

• been implicated in inflammation and cancer metastasis [26], and was chosen as a model glycan for the construction of branched compounds. Glucosamine building block 23, containing C3-levulinoyl (Lev) and C4-Fmoc protecting groups [27], was first reacted with the linker. The glycosylation was followed by

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• substrates [16][17][18][19]. As part of a larger study on the specificity of mannosyltransferases involved in mycobacterial glycan biosynthesis [20][21][22], we had the need for a panel of singly deoxygenated and methylated guanosine diphosphosphate mannopyranose (GDP-Man) derivatives. In developing a

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

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

• that can be of use to glycobiologists, but also to chemists who work on the synthesis or analysis of carbohydrates. This article gives an overview of existing glyco-specific databases and tools, with a focus on their application to glycochemistry: Databases can provide information on candidate glycan

• structures for synthesis, or on glyco-enzymes that can be used to synthesize carbohydrates. Statistical analyses of glycan databases help to plan glycan synthesis experiments. 3D-Structural data of protein–carbohydrate complexes are used in targeted drug design, and tools to support glycan structure analysis

• aid with quality control. Specific problems of glycoinformatics compared to bioinformatics for genomics or proteomics, especially concerning integration and long-term maintenance of the existing glycan databases, are also discussed. Keywords: carbohydrates; databases; glycomics; software

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• applications, in which glycopeptides or glycoproteins serve as tools for biological studies, are reviewed. The importance of specific antibodies directed to the glycan part, as well as the peptide backbone has been realized during the development of synthetic glycopeptide-based anti-tumor vaccines. The fine

• and bacterial infections, tumor growth and metastasis, and auto-immune disorders, all involve glycan cell–cell or cell–external-agent communication [3][4][5]. The availability of structurally defined glycopeptides and glycoproteins, which contain information about the glycan structure and

• excellent reviews [6][7][8][9][10][11][12][13][14][15][16][17][18]. Review Glycopeptide-based vaccines Specific immune recognition, in which the glycan and the peptide backbone contribute to the binding epitope, is of particular interest for the development of safe immunotherapy and immunodiagnostics. Since

Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS

• Martin J. Weissenborn,
• Johannes W. Wehner,
• Christopher J. Gray,
• Robert Šardzík,
• Claire E. Eyers,
• Thisbe K. Lindhorst and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 753–762, doi:10.3762/bjoc.8.86

• or attachment of a hydrophobic tether. The latter has been used highly successfully by the Feizi group as part of the neoglycolipid array technology [8]. More recently, two groups [7][9] have reported the application of hydrophobic tethers for binding to polystyrene slides for glycan analysis

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• , Germany Institute of Microbiology, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4, CZ 14220, Czech Republic 10.3762/bjoc.8.80 Abstract The importance of glycans in biological systems is highlighted by their various functions in physiological and pathological processes. Many glycan

• -Acetyllactosamine (LacNAc; Galβ1,4GlcNAc) structures are important carriers of glycan epitopes, such as ABH or Lewis blood group determinants. Some of these are present on extended poly-N-acetyllactosamine glycans (poly-LacNAc; [Galβ1,4GlcNAc]n) which serve as spacers and additional information carriers [1][2][3][4

• function, and as possible diagnostic markers or therapeutic agents [13][14][15][16]. Naturally occurring poly-LacNAc glycans and furthermore epitopes thereof, such as fucosylated, sialylated and branched glycans, are widely used in the analysis of galectin–glycan interaction in glycan arrays [7][17][18][19

Cyanoethylation of the glucans dextran and pullulan: Substitution pattern and formation of nanostructures and entrapment of magnetic nanoparticles

• Kathrin Fiege,
• Heinrich Lünsdorf,
• Sevil Atarijabarzadeh and
• Petra Mischnick

Beilstein J. Org. Chem. 2012, 8, 551–566, doi:10.3762/bjoc.8.63

• spectroscopy (PEELS). Keywords: cyanoethyldextran; cyanoethylpullulan; ferromagnetic nanoparticles; glycan nanostructures; substitution pattern; Introduction Cyanoethylation has been widely applied to polysaccharides, e.g., to cellulose [1], inulin [2], and starch [3]. Onda reported on cyanoethylation of

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• PIM/LM/LAM substructures are useful biochemical tools to delineate and dissect the fine details of mannose glycophospholipid biosynthesis and their interactions with host cells. We report the efficient synthesis of a series of azidooctyl di- and trimannosides possessing the following glycan structures

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

• overall yields. These aminoethyl glycosides are now readily accessible for incorporation into glycan arrays. Aminoethyl glycosides (1–9) which were synthesised in this study. General reaction scheme for generation of aminoethyl glycosides. X = OAc, Br or Cl. Deprotection protocols. Results of

Synthesis of glycosylated β³-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

• Florian Karch and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2010, 6, No. 47, doi:10.3762/bjoc.6.47

• cell surface glycoproteins is associated with various pathological incidents, e.g., autoimmune and infectious diseases and cancer. In the latter case, unusual glycan structures composed of truncated O-linked oligosaccharides of carcinoma-derived mucin glycoproteins can be used as markers of the

• reduction and acetylation led to the formation of conjugate 2a in 56% yield. During biosynthesis TN antigen acts as an immediate precursor of the TF antigen. As a consequence, a biomimetic approach towards larger TACA structures via stepwise assembly of the glycan chain has been pursued in various antigen

• chain protective groups was achieved upon treatment with a mixture of TFA, triisopropylsilane and water. The resulting partially deblocked glycopeptide 7 was isolated after purification by semi-preparative RP-HPLC in a yield of 36%, based on the loaded resin 5. The final de-O-acetylation of the glycan

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

• through the membrane of eukaryotic cells [3]. Neu5Hex (3) is a new substrate for metabolic glycoengineering which is proposed to be incorporated into the cell surface glycan structures. It was shown that carbohydrates in growth media contribute to alterations in glycosylation patterns in human cells [8

• Neu5Hex 3 guarantees its direct incorporation into the cell surface glycan patterns bypassing metabolic bottlenecks. Furthermore, the described genetic feedback inhibition by sialic acid leading to an accumulation of the fed Neu5Hex 3 ensures an efficient integration into the cell surface glycocalyx. A