Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• glycoengineering, the structural integrity of the saccharide epitope must be maintained and cross-reactivity of the elicited antibodies with the native tumor-associated glycans is required. In this respect, the use of fluorinated TACAs [28][39][40][41][42] is a promising strategy due to the ability of C–F moieties

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

• same molecule was highly reduced [39]. It was then inferred that sialylation of one residue in T. cruzi glycans modulates the susceptibility of nearby sites, and thus, polysialylated complex multiantennary glycans would not be reachable by using the enzyme. Our results suggest that the amount of

• and 120 min gave very similar results (not shown). A steric effect operating on the sialylation of multiple Galp residues has been previously suggested for lactosyl lipids attached to membrane microdomains [40]. The dependence of the amount of disialylation of the divalent glycans on the concentration

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

• purification after the formation of each glycosidic bond, and have enabled the rapid preparation of complex glycans [1]. An alternative strategy for the efficient oligosaccharide formation involves the oligomerization of a single building block that functions both as a glycosyl donor and acceptor. This

• glycosylation methods, and the rapid access to glycans in a single step is a strength of this approach. All of the oligosaccharides reported here have successfully been separated using routine normal-phase silica gel columns on a commercially available flash chromatography system. The oligomerization described

• here is a highly efficient method for homo-oligosaccharide synthesis. We are currently investigating the extension of this approach to targets other than galactans and to the assembly of glycans linked via secondary hydroxy groups. Pyrenebutanol (3) initiated oligomerization. Scope of oligomerization

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• acids; aniline; carbohydrates; glycoconjugates; glycopeptides; Introduction Glycans or other complex oligosaccharide structures, present on the surface of every prokaryotic and eukaryotic cell, are important for a large number of biological recognition processes like, for example, intercellular

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

• infections is still unknown. Over the recent years, advances in the synthesis of complex glycans are rendering accessible a variety of carbohydrate antigens with well-defined chemical structure and devoid of bacterial contaminations which could derive from purification of biological materials [21][22][23][24

• glycans [26][27], lower yields were attained in the present case. This can be explained with the higher solubility in organic solvents of the short structures 11–13 employed in the present study in comparison to other reported oligosaccharides [26][27], which did not allow complete precipitation of the

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

• proteins and mucin-type O-glycans [30]. Here, we show that 1 and 2 can be employed for both labeling of cell-surface glycoconjugates (detected by confocal fluorescence microscopy) and isolated glycoproteins (detected by Western blot). Results and Discussion For the synthesis of the cyclopropene-tagged

• staining. The staining intensity resulting from the galactosamine derivative 2 was in between. Previous work from Bertozzi and coworkers suggests that GlcNAc derivatives such as N-azidoacetylglucosamine (GlcNAz) can only enter cell-surface glycans via less efficient conversion of GlcNAz to N

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• compounds with β-D-talose configuration that are rarely found in nature, an exception being the antibiotic amino glycoside hygromycin B [37]. Aminopyran 17b correlates to β-D-idopyranose; iduronic acid is a component of sulfated glycosamine glycans such as chrondroitin sulfate and heparan sulfate [38]. The

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• ; Introduction Recognition processes between glycans and their receptors are of paramount relevance in several biological phenomena, both in physiological [1][2] and in pathological [3][4][5] conditions. These processes can be exploited in diagnostic tools [6][7], in nanobiotechnology applications [8], and in

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

• and viral infections and are consequently candidates for chemotherapy. The short in vivo half-life of low molecular weight glycans hampered their use but methods for the covalent attachment of PEG have been less exploited. In this review, information on the preparation and application of PEG

• conjugated with both paclitaxel, a potent anticancer drug, and alendronate, a bone-targeting biphosphonate, in order to obtain strong bone tropism and fast drug release [12]. An enzymatic method using a microbial transglutaminase was described for PEGylation of human growth hormone [13]. Glycans have been

• have been focused on polysaccharides or on carbohydrates linked to proteins. A review dedicated to PEGylated chitosan derivatives has been published [22]. In the present review we present different approaches used for modification of glycans by covalent conjugation with PEG reagents, in particular with

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

• assembling glycopeptides demonstrated an antiviral potency which was up to 50 times higher than the activity of peptide-free glycans. Keywords: glycopeptides; influenza virus; multivalent glycosystems; oligoglycine; polyglycine II; self-assembling; tectomers; Introduction Recently, we have synthesized and

• inhibition or the blocking of the binding of the influenza virus with target cells [15]. Monovalent oligosaccharides are incapable of an efficient competition for analogous glycans on the cell surface due to the low binding constant with viral hemagglutinin. An attractive way of increasing the affinity of a

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

• . Keywords: glycosylation; mucin-type oligosaccharides; O-glycans; oligosaccharide synthesis; Introduction Mucins are heavily glycosylated glycoproteins that may be membrane-associated or secreted in gel form and play an important biological role in the respiratory and intestinal tracks [1][2][3]. Mucins

• -deoxy-D-galactose to serine or threonine. This saccharide forms the inner part of the characteristic core oligosaccharides from where glycans are extended through common core (di- and trisaccharide) structures, cores 1–8 [6][7][8]. The mucin-type oligosaccharides identified to date have remarkable

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

• cyclooctenes have been used to examine the role of glycans in such processes such as neurite outgrowth [4], bacterial motility [5], and inflammation [6]. ROMP polymers with pendant reactive functional groups, such as N-hydroxysuccinimide (NHS) or nitrophenyl esters, are useful materials since the pendant

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

• availability of rare monosaccharides that cannot be isolated from natural sources is currently limiting the access to the synthesis and the biological evaluation of complex bacterial cell-surface glycans. Here, we report the synthesis of D- and L-fucosamine building blocks by a de novo approach from L- and D

• glycoproteins and express them on cell surfaces. This evidence makes it particularly relevant especially for the identification of novel antibacterial agents as well as vaccines [7][8][9]. Those bacterial glycans often contain unusual monosaccharides that are not present in the human body. An immune response

• against these cell-surface glycans is the basis for the development of new vaccine candidates against bacterial infections [10][11][12][13]. Our efforts were directed to the development of new vaccine candidates [14][15][16] to prevent bacterial infections, including glycans of the highly pathogenic

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

• ], the need for synthetic tools has prompted synthetic carbohydrate chemists to develop methods for the accelerated synthesis of all types of glycans [9][10][11][12][13][14][15][16][17][18][19]. Automated synthesis of oligosaccharides is beginning to provide molecules for biological evaluation [20][21

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• azide alkyne cycloadditions. In addition, the up-scaling of some particular azide-modified sugars is described. Keywords: click chemistry; glycans; peptoids; polyalkynes; polyamines; solid-phase chemistry; Introduction To date, oligosaccharides have gained more and more interest as potential drugs in

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

• ), CONICET, Buenos Aires (1428), Argentina 10.3762/bjoc.8.241 Abstract The presence of galactofuranoyl units in infectious microorganisms has prompted the study of the metabolic pathways involved in their incorporation in glycans. Although much progress has been made with respect to the biosynthesis of β-D

• products indicates an inverting mechanism. Also lately, galactofuranosyl transferases (GalfT) catalyzing β-Galf incorporation in glycans have been identified. Two bifunctional GalfTs are required for galactan biosynthesis in Mycobacterium tuberculosis, GalfT1 and GalfT2, able to construct both, β-Galf(1→5

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

• Berlin, Germany Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland Institute of Chemistry, Academia Sinica, Taipei, 11529, Taiwan 10.3762/bjoc.8.183 Abstract Sialic acid-containing glycans play a major role in cell-surface interactions with

• ; sialosides; Introduction Sialic acid (Sia) belongs to a family of nonulosonic acids, i.e., monosaccharides equipped with a carboxylic moiety and a nine-carbon backbone, which play a unique role in glycobiology. Sia-containing glycans mediate pathogen invasion [1] and are involved in signalling cascades

• , which have been extensively studied [2]. The distinctive structure of Sia confers special properties to membrane oligosaccharides [3] resulting in sialosides having exceptional biological significance. Rapid access to synthetic sialylated glycans would contribute greatly to the biological studies on

Low-generation dendrimers with a calixarene core and based on a chiral C₂-symmetric pyrrolidine as iminosugar mimics

• Marco Marradi,
• Stefano Cicchi,
• Francesco Sansone,
• Alessandro Casnati and
• Andrea Goti

Beilstein J. Org. Chem. 2012, 8, 951–957, doi:10.3762/bjoc.8.107

• enhance the avidity of interactions between glycans and lectins [15]. Some glycocalixarenes have shown remarkable inhibition properties towards galectins [21][22] or Pseudomonas Aeruginosa lectin [23], the inhibition ability being dependent on the macrocyclic conformation and presentation of the glycoside

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

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

• ; Introduction Carbohydrates, often referred to as glycans, differ from other biopolymers such as proteins or nucleic acids in various ways. The number of different monosaccharides that are present in naturally occurring glycans is significantly higher than the number of proteogenic amino acids, or of

• nucleotides that form DNA or RNA strands [1][2]. Furthermore, the monosaccharides can be linked to each other in several ways, including the possibility to form branched structures. Another important difference between glycans, on the one hand, and proteins and nucleic acids, on the other hand, is visible in

• amounts. If specific and well-defined glycans are required for experiments such as glycan arrays [4], they have to be synthesized chemically [5]. The special features of carbohydrates not only pose problems for their wet-lab analysis but also for computational approaches that deal with carbohydrates

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

• cell-surface binding events, such as cell growth and differentiation, cell proliferation, cell adhesion, binding of pathogens, fertilization and immune responses [1][2]. Furthermore, glycans assist in intracellular protein folding and transport. Pathogenic processes, such as chronic inflammation, viral

• glycans per repeat, and the sites for glycan attachment on the MUC1 peptide backbone were explored. For the induction of a strong and specific immune response, different immuno-stimulants were connected to the mucin glycopeptides. Among the immuno-stimulants, the Toll-like receptor 2 (TLR2) ligand

• β-subunit of human follicle-stimulating hormone (hFSH) glycoprotein was prepared, containing two complex type N-glycans, modified with core fucose and terminal sialic acid glycan residues [57]. The FSH β-subunit was prepared by sequential native chemical ligation. Initially, a larger C-terminal

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

• of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 3/4, 24098 Kiel, Germany 10.3762/bjoc.8.86 Abstract Glycans functionalised with hydrophobic trityl groups were synthesised and adsorbed onto polystyrene and glass slides in an array format. The adsorbed glycans could be

• . Initially, simple alkyl chains were used as tethers [9] but more recently, Wong and co-workers improved on this technology by using trityl-derived glycans, which are easily attached to glycans and were reported to bind strongly to polystyrene (Figure 1A) [7]. The attachment of glycans to the surface was

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

• epitopes on glycoproteins and glycolipids are based on N-acetyllactosamine units (LacNAc; Galβ1,4GlcNAc) and often present on extended poly-LacNAc glycans ([Galβ1,4GlcNAc]n). Poly-LacNAc itself has been identified as a binding motif of galectins, an important class of lectins with functions in immune

• response and tumorigenesis. Therefore, the synthesis of natural and modified poly-LacNAc glycans is of specific interest for binding studies with galectins as well as for studies of their possible therapeutic applications. We present the oxidation by galactose oxidase and subsequent chemical or enzymatic

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

• important component of glycoprotein glycans and also a substrate for sialyltransferases to generate biologically important sialyllactosides. The aminoethyl lactoside 16 was prepared in greatest yield from the bromide and attempts to prepare 16 directly from the acetate using BF3·Et2O as the activator only

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

• -surface glycans. Although it has been known for many years that sialic acids are involved in myriads of interaction processes including viral infections such as the emerging flu variants, their biological role on cell surfaces of different cell lines and at different development states remains unclear. As

• new techniques for probing glycans have evolved only relatively recently, more information about the fundamental biological functions of carbohydrate structures can be obtained. Therefore we introduced metabolic glycoengineering of the human larynx carcinoma cell line HEp-2. The incorporation and cell

• cyclooctyne (DIFO) and cell-surface azido-glycans introduced recently has been proven to be suitable for in vivo labelling [14][17][18]. Experimental 2-azidoacetylamino-2-deoxy-1,3,4,6-tetraacetyl-β-D-glucopyranoside (16) was synthesized as described previously [9] N-(1R,2R,3S,4R)-Hex-5-yonic acid (2,3,4,5

Synthesis in the glycosciences

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2010, 6, No. 16, doi:10.3762/bjoc.6.16

• . Since the isolation of those complex glycans which are active in cellular communication is problematic, oligosaccharide synthesis is an important area of research. Moreover, what Professor Hans Paulsen, one of the greatest exponents of glycoside synthesis, observed in 1982 [2] still holds true today