Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• B cell epitopes used was the J8-peptide antigen. This epitope was identified from the conserved C-terminal region of the M protein (a cell surface protein and a major virulence factor) of S. pyogenes [19]. For comparison purposes, the J8 epitope was also employed in the current studies. The

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• rendering O-antigen-based vaccines ineffective. But the conservation of the A-band polysaccharide even in the colonized form makes this repeating unit a viable candidate for A-band polysaccharide-based vaccines which can avoid the vulnerability applicable to their O-antigen-based counterparts [16]. Hence

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• Transfusion, Leiden University Medical Centre, P. O. Box 9600, 2300 RC Leiden, The Netherlands 10.3762/bjoc.10.148 Abstract The covalent attachment of an innate immune system stimulating agent to an antigen can provide active vaccine modalities capable of eliciting a potent immune response against the

• incorporated antigen. Here we describe the design, automated synthesis and immunological evaluation of a set of four muramyl dipeptide–peptide antigen conjugates. Muramyl dipeptide (MDP) represents a well-known ligand for the intracellular NOD2 receptor and our study shows that covalently linking an MDP-moiety

• TLR2-ligand Pam3CSK4 [13][14], TLR7-ligand 7-hydroxy-8-oxoadenine [15] or TLR9-ligand CpG DNA [13] were covalently bound to a model antigen, an ovalbumin derived peptide comprising the MHC I epitope SIINFEKL, embedded in a longer peptide motif (DEVSGLEQLESIINFEKLAAAAAK, DEVA5K) [13][16]. We revealed

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• manufacturer’s recommendations. A virus equivalent to 4 ng of p24 capsid protein (quantified by an antigen-capture assay; Innogenetics, Belgium) of the NL4-3 strain of HIV-1 was chosen as the lowest level of viral input sufficient to give a clear luciferase signal within the linear range at day 3 post-infection

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• residues of mannose for DC targeting and one residue of an immunogenic mimetic of a carbohydrate melanoma associated antigen. The immunological assays demonstrated that the glycodendron 5 is able to induce human immature DC activation in terms of a phenotype expression of co-stimulatory molecules

• Cancer immunotherapy [1] attempts to induce a long-lasting antitumor immunity and boost the immune response overcoming the tumor induced immunosuppression. The immune system, apart from very few exceptions, fails to taking an adequate course of action against tumors. Tumor cells are indeed poor antigen

• ][6]. In this context, the discovery of human cancer-specific antigens [7][8] has represented a challenge for the design of tailored cancer vaccines and it has allowed the development of antigen-specific immunotherapy strategies. This approach offers the advantage that the immune response induced by

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

• the α-sialyl linkage in 6 was also unambiguously confirmed by the NMR data (H-3eq’ δ = 2.25 ppm, Δδ [H-9’a–H-9’b] = 0.36 ppm) [24]. Then, carbohydrate antigen 1 was obtained also by catalytic hydrogenolysis with Pd/C in methanolic HCl of 18 to yield the amine-containing derivative in 98% yield. To

Straightforward synthesis of a tetrasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O16

• Manas Jana and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 1757–1762, doi:10.3762/bjoc.9.203

• Manas Jana Anup Kumar Misra Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata-700054, India, Fax: 91-33-2355 3886 10.3762/bjoc.9.203 Abstract A straightforward synthesis of the tetrasaccharide repeating unit of the O-antigen of Escherichia coli O16 has been

• stereoselective. Keywords: Escherichia coli; glycosylation; lipopolysaccharide; O-antigen; tetrasaccharide; Introduction Neonatal meningitis is a serious concern in developing countries [1]. The symptoms associated with this disease are unspecific and may ultimately lead to sepsis [2]. The common cause of the

• containing D-glucosamine, L-rhamnose, D-glucose and D-galactofuranose moieties in a 1:1:1:1 ratio (Figure 1). The emergence of multi drug resistant bacterial strains forces medicinal chemists to develop new approaches to combat bacterial infections. Since the structure of the O-antigen influences the

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• validation using a panel of known receptor and kinase-based counter screens [7]. Because activation of NF-κB is known to be initiated through protein kinase C (PKC), we hypothesized that selectivity could be possible by the fact that PKC activation occurs downstream from cell membrane antigen and growth

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

• employed in the successful synthesis of a sialyl LewisX tetrasaccharide [15] and a sialyl Tn antigen [16]. In the search for a linker suitable for the solid-phase synthesis of complex glycosaminoglycans (GAGs) [17][18], we designed a new acylsulfonamide safety-catch linker that combined the advantageous

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

• Abhijit Sau and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2012, 8, 2053–2059, doi:10.3762/bjoc.8.230

• yielding and stereoselective. Keywords: Escherichia coli; glycosylation; lipopolysaccharide; O-antigen; tetrasaccharide; Introduction Infantile diarrhoea is one of the major causes of morbidity and mortality in infancy in developing countries [1]. Among several factors, Escherichia coli (E. coli

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• Christopher J. Moore France-Isabelle Auzanneau Department of Chemistry, University of Guelph, 50 Stone Rd. East, Guelph, Ontario, N1G 2W1, Canada 10.3762/bjoc.8.126 Abstract Three analogues of the Lex trisaccharide antigen (β-D-Galp(1→4)[α-L-Fucp(1→3)]-D-GlcNAcp) in which the galactosyl residue

• yields. Keywords: chlorodeoxygalactose; fluorodeoxygalactose; Lewis X analogues; oligosaccharide synthesis; Introduction A glycolipid displaying the dimeric Lex hexasaccharide (dimLex) has been identified as a cancer associated carbohydrate antigen, particularly prevalent in colonic and liver

• ) have been shown to recognize this Lex antigenic determinant as it exists in the hexasaccharide [1][2][3][4][5][6]. Therefore, as our group embarks on the development of a therapeutic anticancer vaccine utilizing the Tumor Associated Carbohydrate Antigen (TACA) dimLex as a target, an important factor to

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

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

• of nuclear magnetic resonance (NMR) experiments that had been performed to elucidate the structures. Other sources of NMR data are SugaBase [36], which similar to CarbBank is no longer maintained, GlycoBase (Lille), Escherichia coli O-antigen Database (ECODAB) [22], and Glycosciences.DB [31], the

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

• the discovery, by Springer et al., that glycoproteins on the outer cell membrane of epithelial tumor cells have an altered glycosylation consisting of the Thomsen-Friedenreich (T-) antigen and its precursor TN-antigen structure, the synthesis and evaluation of anti-tumor vaccines have been a topic of

• T-antigen, or a difluoro-T-antigen on different positions in the tandem repeat (6–10), showed that high antibody titers were induced in almost all of the immunized mice. Evaluation of the generated antibodies provided evidence that specific immune responses were elicited towards the MUC1 antigens

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• ]. Furthermore, the overexpression of the charged blood group antigen sialyl Lewisx consisting of the terminal NeuNAcα2-3Galβ1-4(Fucα1-3)GlcNAc-group is correlated with carcinogenesis. It is recognized and bound by selectins, which are a subgroup of lectins that play an important role as cell-surface molecules

Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel

• Elena A. Khatuntseva,
• Vladimir M. Men’shov,
• Alexander S. Shashkov,
• Yury E. Tsvetkov,
• Rodion N. Stepanenko,
• Raymonda Ya. Vlasenko,
• Elvira E. Shults,
• Genrikh A. Tolstikov,
• Tatjana G. Tolstikova,
• Dimitri S. Baev,
• Vasiliy A. Kaledin,
• Nelli A. Popova,
• Valeriy P. Nikolin,
• Pavel P. Laktionov,
• Anna V. Cherepanova,
• Tatiana V. Kulakovskaya,
• Ekaterina V. Kulakovskaya and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2012, 8, 763–775, doi:10.3762/bjoc.8.87

• bark, or without an adjuvant, and the specific anti-3’SL IgM and IgG responses were evaluated. For saponins 1 and 2, a significant specific response was observed in comparison with the control vaccine formulation with antigen alone (Table 6). High serum titers of IgM and IgG antibodies were registered

• in the vaccination with compound 1 as adjuvant, though the IgG level did not achieve the level measured in the experiment with saponin from Quillaja bark. Titers of those antibodies in the experiment with saponin 2 were rather low. We can conclude, that in combination with 3’SL-KLH, antigen compound

• collected on day 91 post-inoculation (p.v.) of the first dose of vaccine and pooled. The titers for IgG and IgM against α-NeuAc-(2→3)-β-Galp-(1→4)-β-Glcp were determined in an indirect ELISA as previously described [31]. ELISA plates (96-well, Nunc Maxisorp) were coated with a cover polyacrylamide antigen

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

• -antigens (β1,6-branched poly-LacNAc) [58][59]. The I-antigen structures have so far been synthesised by chemical routes [60][61]. A similar coupling of oligosaccharides has already been shown by Rodriguez et al. on peptides, but no branching site in the glycans was introduced in their study [35]. In

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• the cytoplasm fluid membrane together with ubiquitous phospholipids, without inducing stereochemical stress. Keywords: cytoplasm membrane; glycolipid antigen; glycosylation; mycoplasma; stereochemistry; Introduction Mycoplasmas constitute a family of gram-positive microbes lacking rigid cell walls

Convergent synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9

• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2011, 7, 1182–1188, doi:10.3762/bjoc.7.137

• Abhishek Santra Anup Kumar Misra Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata-700054, India; Fax: 91-33-2355 3886 10.3762/bjoc.7.137 Abstract A convenient synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9 has been

• glycoside in high yield. Keywords: diarrhea; glycosylation; O-antigen; oligosaccharide; Shigella boydii; Introduction Diarrhoeal disease is a common cause of death in the tropical countries and it is the second mostly causing infant deaths worldwide. Shigella is one of the well-studied human pathogens

• the presence of acidic constituents (e.g., uronic acid, pseudaminic acid etc. or lactic acid, pyruvic acid etc.) in their structures [6][7]. Recently, L’vov et al. reported the structure of the O-antigen of Shigella boydii type 9, which is a tetrasaccharide repeating unit containing a D-glucuronic

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• its antigen, and that his statement (quoted above) regarding complementarity between an enzyme and the “activated complex” of the catalysed reaction is in turn followed by this sentence [3]: “If the enzyme were completely complementary in structure to the substrate, then no other molecule would be

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• College Dublin, Belfield, Dublin 4, Ireland, Phone: +353 17162318 10.3762/bjoc.6.80 Abstract Background: In bacteria with truncated lipopolysaccharide structures, i.e., lacking the O-antigen polysaccharide part, core structures are exposed to the immune system upon infection and thus their use as

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

• bioavailability for tumour immunotherapy. Towards this end, TN and TF antigen conjugates O-glycosidically linked to Fmoc-β3-homo-threonine were prepared in good yield via Arndt–Eistert homologation of the corresponding glycosyl α-amino acid derivative. By incorporation of TN-Fmoc-β3hThr conjugate into the 20

• antigen) linked to β3-homo-serine are known. Despite their importance as specific tumour antigens, conjugates of Fmoc-β3hSer and Fmoc-β3hThr carrying larger TACA structures such as the Thomsen–Friedenreich antigen (TF) or its sialylated variants (α2-6sTF and α2-3sTF) have not been reported to date. By

• presenting orthogonally protected TN and TF antigen conjugates of Fmoc-β3hThr (Figure 1) as well as a first α/β-hybrid glycopeptide analogue comprising the 20 amino acid tandem repeat sequence of the human mucin MUC1, we describe preliminary results of our synthetic efforts towards the preparation of mucin

Convergent syntheses of Le^X analogues

• An Wang,
• Jenifer Hendel and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2010, 6, No. 17, doi:10.3762/bjoc.6.17

• efficient and convergent preparation of these three Lex analogues. Keywords: Birch reduction; convergent synthesis; desulfurization; Lewis X; Introduction Our group is involved in the design of new anti-cancer vaccines based on the Tumor Associated Carbohydrate Antigen (TACA) dimeric Lex (dimLex) [1][2][3

• ][4][5][6]. This tumor specific antigen consists of a hexasaccharide that displays the Lex trisaccharide antigen linked to O-3″ of the galactose residue of another Lex trisaccharide. Since it was first characterized [7][8], the Lex antigenic determinant, β-D-Galp(1,4)[α-LFucp(1,3)]-D-GlcNAcp, has been

• addition to the Lex trisaccharide we are also interested in preparing fragments of the dimLex antigen, we examined the glycosylation at O-4 of glucosamine glycosyl acceptors with galactosyl donor 8, which is chloroacetylated rather than acetylated at O-3. Finally, we also investigated the reactivity