N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• used as detergents, surfactants and emulsifiers. Moreover, they display a wide range of pharmacological activities, including antifungal, antiparasitic, antiinflammatory, antibacterial, and antitumor activities [2][3][4][5]. No wonder, saponins have been evaluated as vaccine adjuvants [6]. Despite the

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

• scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible

• prevention and cure. Thus, administration of a therapeutic vaccine will trigger an effective immune response to allow eradication of tumor cells, which might have evaded surgery or have metastasized into the bloodstream [5]. A prerequisite for this approach is inter alia an efficient distinction of malignant

• antibodies elicited from this vaccine were found to cross-react with native TF epitopes of MCF-7 cancer cells. Similarly, Yang et al. found that fluorinated sTn antigen conjugates were significantly more immunogenic than their natural congeners and also elicited antibodies cross-reactive to sTn-positive LS-C

Effects of RAMEA-complexed polyunsaturated fatty acids on the response of human dendritic cells to inflammatory signals

• Éva Rajnavölgyi,
• Renáta Laczik,
• Viktor Kun,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3152–3160, doi:10.3762/bjoc.10.332

• information to other cell types lead to the notion that different subtypes and subsets of DC are central regulators of both innate and adaptive immunity and thus they can also be harnessed for vaccine development [33] and also for immunotherapeutic interventions [34]. By using high throughput approaches we

Synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4

• Pintu Kumar Mandal

Beilstein J. Org. Chem. 2014, 10, 2724–2728, doi:10.3762/bjoc.10.287

• bacterial O-antigens have been chosen for the development of glycoconjugate vaccine candidates against infectious diseases [13][14][15][16]. As a consequence, a significant quantity of oligosaccharides is required to evaluate their immunological properties for detailed understanding of the role of O

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

• , 53100 Siena, Italy 10.3762/bjoc.10.247 Abstract A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX) is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS) fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as

• promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer) to CRM197. Moreover, improvements in

• incidence decreased in most meningitis belt countries following the introduction in 2010 of a monovalent MenA conjugate vaccine (MenAfriVac) [11][12], an increase in MenX cases has been observed. Recently a study revealed that in Burkina Faso the levels of MenX carriage after the introduction of the MenA

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

• by the preparation of a second vaccine candidate which incorporated an additional promiscuous T-helper epitope. Keywords: amino acid lipidation; cycloadditon reaction; multivalent glycosystems; peptide vaccine; tetrapropargyl glucopyranose; Introduction Vaccination is often the most effective and

• derived from GAS. The vaccine constructs consisted of the LCP adjuvanting moiety, and a carbohydrate core bearing four copies of a GAS B cell epitope [11][15][16][17][18]. When administered to B10.BR (H-2k) mice, the carbohydrate-based LCP vaccines elicited high serum IgG antibody titres [11]. One of the

• previously reported carbohydrate-based vaccine constructs [11] were prepared by a divergent approach, where the carbohydrate core was coupled to the resin-bound LCP adjuvanting moiety, followed by stepwise synthesis of the B cell epitopes using solid-phase peptide synthesis (SPPS). Using this divergent

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

• tetrasaccharide, α-D-Rhap-(1→2)-α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap [17] and a trisaccharide, α-D-Rhap-(1→3)-α-D-Rhap-(1→2)-α-D-Rhap [18] related to the A-band polysaccharide of P. aeruginosa were made with a view to develop glycoconjugate vaccines, but none have ultimately materialized into valid vaccine

• candidates. Thus, we targeted the trisaccharide [α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap] as our synthetic goal toward construction of a probable vaccine candidate against P. aeruginosa. The synthesis of the D-rhamnose-based oligosaccharide from the D-mannose motif has received substantial attention over the

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

• (PRR-L) covalently bound to antigenic proteins and oligopeptides in the development of new (semi)synthetic vaccine modalities [3][4][5][6][7][8][9]. For instance, the group of Boons investigated a three-component conjugate containing a tumor-associated glycopeptide and a T cell epitope covalently bound

• that these can display a more favorable uptake profile than the relatively polar MDP-conjugates (2–5) described here. Conjugates of these lipophilic MDPs can therefore be attractive vaccine modalities and efforts are currently underway in our laboratory to investigate these. MDP-antigen conjugates 2–5

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

• adenovirus coat for vaccine development [5], antibodies or antibody fragments to prolong their circulating half-lives in vivo [6] and selective alkylation and acylation of amino groups in a somatostatin analog using two different PEG reagents [7]. Also, PEGylation of low molecular weight drugs in order to

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

• preventions, the strategies used to inhibit viral replication in human CD4+ T cells consist in the highly active antiretroviral therapy (HAART) [3] and the design of a vaccine that should protect people among all the different HIV strains [4][5]. Although great results have been obtained by the use of the

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

• of a potential vaccine against melanoma disease [28]. The GM3 metabolite, named GM3-lactone 2 (Figure 1) has also been found in melanoma cells as a minor component [29][30]. Although more immunogenic than GM3-ganglioside 1, GM3-lactone 2 failed as an immunostimulant because under physiological

• kind of compounds based on multivalent ditopic glycodendrons might be used to address the preparation of a synthetic vaccine against melanoma. In addition, this strategy might be applied to other diseases in immunotherapy. Experimental Reagents were purchased from Sigma–Aldrich and Fluka and were used

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

• 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

• to stimulate an antibacterial response in the host organism [17][18][19][20][21][22][23]. Access to differentially protected D- and L-fucosamine building blocks, which can be used in preparing the corresponding glycans, is instrumental for the evaluation of oligosaccharide-based vaccine candidates

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

• ]. Glycosylamines are used also as enzyme inhibitors and vaccine precursors [18][19][20][21], and in glycopeptide synthesis [22][23] and in glycodendrimers and glycoclusters [24][25]. There are four structural isomers of glycosyl-thiosemicarbazides according to the location of the glycosyl residue on the

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

• ) 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

• weakly recognise Lex trisaccharide antigen [1][2][3][4][5][6]. With this in mind, we focus our research on the discovery of analogues of dimLex that can be used as safe vaccine candidates. Ideally, these analogues should display the internal epitopes that are recognized by anti-dimLex SH2-like antibodies

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

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

• templates in vaccine development [67][68][69][70], and glycomimetics that block specific enzymes or lectins can be used for therapeutic purposes [71][72][73][74][75][76][77]. The Glycan Pathway Prediction (GPP) tool of the RINGS portal [78] can be used to predict glycans that can be obtained with a given

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

• present in the vaccines. FACS analysis with serum antibodies induced by the MUC1 vaccines 7–10 showed that they all recognize MCF-7 breast-cancer cells. The serum from mice immunized with vaccine 9 was further evaluated through mammary carcinoma tissue-staining experiments. A gradual increase of the

• sialyl-T MUC1 glycopeptides (2, 11, 12) were prepared and fully deprotected. Peptide synthesis was followed by fragment condensation employing HATU and HOAt and after additional deprotection steps, resulting in the formation of the lipopeptide vaccine constructs 14–16. Immunization of the vaccines in

• vaccines, containing an extra tetanus toxoid T-cell peptide epitope, showed a stronger immune response when the MUC1 peptides were glycosylated, whereas the nonglycosylated two- and three-component vaccines did not show any difference in antibody titers [36]. Recently, a three-component vaccine consisting

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

• obtained saponins were elucidated by a combination of mass spectrometry and 2D NMR spectroscopy. A study of acute toxicity, hemolytic, anti-inflammatory, immunoadjuvant and antifungal activity was carried out. Both saponins 1 and 2 were shown to exhibit immunoadjuvant properties within the vaccine

• stable fraction QS-21 [8], which is included now into a vast range of pilot vaccine compositions against viral infections [11][12][13] and cancer [14][15][16][17]. Meanwhile, the search for abundant, nontoxic, stable and individual saponin adjuvants is still urgent. This explains the enormous interest in

• vaccine neoglycoconjugate α-NeuAc-(2→3)-β-Galp-(1→4)-β-Glcp-KLH (3’SL-KLH) on the basis of 3’-sialyllactoside (3’SL) ligands and keyhole limpet hemocyanin (KLH) protein carrier [26]. Four groups of mice were immunized with 40 µg of 3’SL-KLH together with 50 µg of compound 1 or 2, or saponin from Quillaja

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• developing countries. This disease affects 40% of the global population, causing an annual mortality of one million people [1]. Despite recent advances in the development of a vaccine against malaria, chemotherapy remains the most viable alternative towards treatment of the disease [2]. In light of the rapid

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• genotypes in the world’s industrialized nations, genotype 1 being the most prevalent, followed by genotype 2 and 3. Due to the poor toleration of the current therapy, and the lack of an appropriate vaccine, researchers working on strategies for developing antivirals have tried to attack viruses at every

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

• , i.e. the bacteria express common human carbohydrate structures on their surface that the host recognises as self-structures and do not produce antibodies against. Construction of a glycoconjugate vaccine against NTHi is thus quite complex. Carbohydrate structures that are both exposed on the surface

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

• tumourigenic process and as target structures for cancer immunotherapy [5]. Over the last years, mucin-type glycopeptides decorated with tumour-associated carbohydrate antigens (TACA) have been shown to trigger strong humoral immunity within molecularly defined vaccine prototypes [6][7][8][9][10]. However, the

• limited metabolic stability of the glycopeptide conjugates represents a major obstacle for the development of efficient carbohydrate-based vaccines. Various strategies towards the incorporation of non-natural hydrolysis resistant carbohydrate analogues into vaccine constructs have been pursued. For