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

• Laura Morelli Damiano Cancogni Marta Tontini Alberto Nilo Sara Filippini Paolo Costantino Maria Rosaria Romano Francesco Berti Roberto Adamo Luigi Lay Dipartimento di Chimica and ISTM-CNR, Universita degli Studi di Milano, via Golgi 19, I-20133 Milano, Italy Novartis Vaccines, Via Fiorentina 1

• ; vaccines; Introduction Neisseria meningitidis is an encapsulated, aerobic gram-negative diplococcus which causes significant morbidity and mortality in newborns, children and young adults worldwide through meningitis and/or septicemia. Although sporadic cases occur in Europe and North America, major

• conjugate vaccine [14]. Undoubtedly the recent increase of MenX infections has led to take in consideration this emerging serogroup for the development of new meningococcal vaccines [15][16]. Recently it has been reported that coupling long chain oligosaccharides from MenX CPS to the nontoxic mutant of

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

• , Australia 10.3762/bjoc.10.181 Abstract A novel convergent synthetic strategy for the construction of multicomponent self-adjuvanting lipopeptide vaccines was developed. A tetraalkyne-functionalized glucose derivative and lipidated Fmoc-lysine were prepared by novel efficient and convenient syntheses. The

• economic long-term way to prevent disease [1]. Through vaccination, successful outcomes have been achieved for diseases such as smallpox, polio and diphtheria, thus providing motivation for the development of superior vaccines for other diseases. Traditionally, vaccines consisted of killed or live

• patients [2][3]. To overcome such issues, subunit vaccines, which contain only the minimum B and T cell peptide epitopes, were developed. However, when such peptide epitopes are administered alone, they are poorly immunogenic. This is due to their instability in the presence of proteases, and due to the

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• requires an intermediate purification, a sequential one-pot assembly can be performed in good yields by starting with thiol–chloroacetyl coupling. This process is currently used in our laboratory for the construction of mutliantigenic synthetic vaccines against cancers. Experimental General details. All

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

• 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

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

• ][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

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• ideal starting material for glycoconjugate vaccines against the enteropathogenic bacterium Shigella sonne [80]. Enzymatically, L-glucose can be synthesized by isomerizing L-fructose (Scheme 13) catalyzed by D-xylose isomerase from Candida utilis [81] or whole cells of a mutant Klebsiella pneumoniae

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

• 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

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

• backbones, or mimics thereof, offer further possibilities to study protein-binding events. Keywords: glycopeptide binding; glycopeptides; glycoprotein synthesis; solid-phase peptide synthesis; synthetic vaccines; Introduction The majority of human proteins are co- or post-translationally modified by mono

• glycosylation sites, is valuable for functional biological studies. Glycopeptides have, for instance, been applied to evaluate the role of conformational and proteolytic stability [6]. In other studies, synthetic glycopeptides have been employed in vaccines to induce specific immune responses or for the

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

• development not only of new tools for tumor diagnosis and monitoring but also in the design of new anticancer drugs [8]. Attempts have been made to mount an immune response against tumor oligosaccharides by carbohydrate vaccines [9] and also to inhibit adhesive processes, such as the interaction between

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

• of immunotherapy methods. Among the most efficient saponin adjuvants are the components of a complex mixture of triterpenoids extracted from the bark of Quillaja saponaria Molina, which are used in veterinary vaccines [4]. One of the best known products of this origin is the less toxic and more

Synthesis of heteroglycoclusters by using orthogonal chemoselective ligations

• Baptiste Thomas,
• Michele Fiore,
• Isabelle Bossu,
• Pascal Dumy and
• Olivier Renaudet

Beilstein J. Org. Chem. 2012, 8, 421–427, doi:10.3762/bjoc.8.47

• methods, we decided to explore two chemoselective strategies to achieve this purpose. We first selected the oxime ligation since we have previously used this approach successfully for the preparation of sophisticated molecular systems, such as synthetic vaccines [27][28], immunomodulators [29], lectin

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

• carbohydrate surface antigens in glycoconjugate vaccines can be considered and investigated. One such suggested structure from Haemophilus influenzae LPS is the phosphorylated pentasaccharide 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. Results: Starting from a spacer

• the title compound have been constructed to allow further use in biological experiments. Keywords: conjugate vaccines; glycoconjugates; Haemophilus influenzae; lacto-N-neotetraose; oligosaccharide synthesis; thioglycosides; Introduction Haemophilus influenzae are Gram-negative bacteria divided into

• six serotypes, a–f, related to the structure of the capsular polysaccharide usually surrounding the bacterium [1]. Among these serotypes, type b is the cause of the most severe diseases, i.a. meningitis and pneumonia. However, there are now several commercial vaccines against this serotype that have

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

• carbohydrate antigens (TACA) have proven to be important target structures for the development of molecularly defined anti-cancer vaccines. The strategic incorporation of β-amino acid building blocks into such mucin-type sequences offers the potential to create pseudo-glycopeptide antigens with improved

• amino acid tandem repeat sequence of MUC1 using sequential solid-phase glycopeptide synthesis, a first example of a mixed α/β-hybrid glycopeptide building block was obtained. The latter is of interest for the development of novel glycoconjugate mimics and model structures for anti-cancer vaccines with

• 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

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