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

• the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide. Keywords: carbohydrates; glycoconjugates; immunology; multivalent glycosystems Neisseria meningitidis

• activated oligomers. To increase the yield of this step, compounds 11–13 were recovered from the dimethylsulfoxide–ethyl acetate mixture by evaporation of ethyl acetate and addition of fresh ethyl acetate at 0 °C. The newly precipitated activated carbohydrates were freeze-dried and coupled to the protein

• well-defined carbohydrates for the development of a glycoconjugate vaccine. While, at the present dose and carbohydrate loading, conjugates of the synthetic MenX PS monomer and dimer with CRM197 were poorly antigenic, the conjugated trimer resulted in the minimal structure eliciting antibodies that can

Multivalent glycosystems for nanoscience

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2014, 10, 2345–2347, doi:10.3762/bjoc.10.244

• Thisbe K. Lindhorst Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 3/4, 24098 Kiel, Germany 10.3762/bjoc.10.244 Keywords: multivalent glycosystems; Carbohydrates constitute the most abundant class of biomolecules on Earth. They are “global

• surface. Hence, carbohydrates are like Alice’s Wonderland—they can assume any role. They can be big or small, sweet or sour, silent or explicit, crucial or, less often, irrelevant. What we do understand, however, is that carbohydrates are essential to life, both in a state of health and in the case of

• disease. Consequently, the glycosciences have gained great respect in chemistry and biology. It is now generally considered important to be able to synthesize carbohydrates and glycoconjugates, to purify and analyze their structures, and to advance our understanding of the biology of carbohydrates in

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• -biosynthetic lipophilization of various biomolecules such as of proteins and carbohydrates is of decisive importance for the correct function of the cell [1]. With the recent discovery of geranylated tRNAs in bacteria [2] the interest in so-called lipo-oligonucleotides (LONs) has grown tremendously [3][4]. 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

• higher fluorescence staining of cell-surface glycoconjugates, the glucosamine derivative gave higher labeling efficiency with protein preparations containing also intracellular proteins. Keywords: bioorthogonal chemistry; carbohydrates; cyclopropenes; inverse-electron-demand Diels-Alder reactions

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• azide reduction followed by final deacetylation using methanolic sodium methoxide furnishes the title compounds. Keywords: allylation; carbohydrates; epoxidation; indium; multivalent glycosystems; organocatalysis; Introduction The indium-mediated allylation of carbonyl compounds has proven to be a

• valuable tool for carbon chain elongation [1][2][3] in order to access rare, biologically active carbohydrates [4][5][6][7][8]. Herein we report the extension of this method towards the field of higher aminosugars by additionally applying a stereoselective epoxidation–azide opening strategy. The resulting

• allowing for an evaluation of structure–activity relationships. Results and Discussion We started our reaction sequence with an indium-mediated allylation of unprotected carbohydrates using D-arabinose (1a), D-galactose (1b) and D-glucose (1c) as starting materials. The Barbier-type chain elongation

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• carbohydrates. In the context of our studies on the synthesis of sugar amino acids structurally related to iminosugar mannojirimycin (a strong inhibitor of α-mannosidase), we have recently prepared, by applying the Grignard reaction, several branched sugar carbinols as intermediates for subsequent oxidation to

• ) groups, respectively. Finally, the o-tolyl structure and benzyl structure of the moieties at C-5 atom of ketone 8 (Figure 1) and ketone 9 (Figure 2), respectively, (the numbering of the atoms is in accordance with the numbering recommended by the IUPAC Nomenclature of Carbohydrates [23]) was

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• a d-methanol–CO2 complex occurred through Lewis acid–base interactions over hydrogen-bonding interactions [80]. Oxygenated hydrocarbon-based molecules have also been designed for use in CO2 by Raveendran et al., where selected carbohydrates were solubilised indicating the potential that they hold as

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

• mimetics; hydrogenolysis; multivalent glycosystems; 1,2-oxazines; samarium diiodide; Suzuki cross-coupling; Introduction Carbohydrates are the class of biomolecules with the highest structural diversity [1][2]. Specific carbohydrates are responsible for cell-type specific interactions [3] and they are

• involved in different diseases such as cancer [4], inflammation [5], and infections [6]. However, the use of carbohydrates as drugs has been strongly limited due to the hydrolytic lability of the glycosidic bond [7] and the weak binding affinities of single molecules. With the development of artificial C

• -glycosides which possess structural and functional aspects of the corresponding carbohydrates, these disadvantages can be overcome, resulting in an improved bioavailability, higher affinities and improved selectivities [8][9][10][11][12][13]. Recent results indicate that divalent rigid carbohydrate

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

• gave the novel carbohydrate building block 1 in 31% overall yield (Scheme 2). Similar carbohydrates have been used for the preparation of glycoclusters for lectin binding [25][26][27][28] and as scaffold carriers of multiple peptide antigens [17][29]. However, the synthesis of the new carbohydrate

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

• carbonyl group at the termini has been carried out. The carbonyl group has been exploited for the multivalent conjugation to a sample saccharide by reductive amination and alkoxyamine conjugation. Keywords: bis-MPA; carbohydrates; dendrons; levulinic acid; multivalency; multivalent glycosystems

• understand these phenomena, dendrimers and dendrons have been developed to provide multivalent glycoconjugates [13][14]. Here, we propose the synthesis of novel dendron structures which allow for the multivalent conjugation of carbohydrates via carbonyl chemistry. Results and Discussion The

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• activity [6]. Furthermore, Gal-3 can act as a competitive inhibitor against Gal-1 which, on the other side, induces anoikis of tumor cells [7][8]. Glycocalixarenes [9][10][11][12], calixarenes [13][14][15] adorned with carbohydrates at the upper and/or at the lower rims, have been demonstrated to be

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• dedicated to the construction of photoactive glycoligand incorporating a light-sensitive unit [12][13][14][15]. The possibility to photomodulate the complexation of a ligand could lead to a deeper understanding of the typically multivalent binding processes of carbohydrates to proteins, in addition to offer

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented. Keywords: amphiphiles; carbohydrates; click chemistry; high

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

• protein:carbohydrate systems using a wide assortment of scaffolds and carbohydrates [2]. As research with multivalent glycosystems advances, one important target for potential therapy and understanding is the galectin family of proteins [3]. Members of the galectin family share a common conserved sequence carbohydrate

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• 9-mer 12, 17, and 21 were determined by pulsed-field-gradient-stimulated echo (PFG-STE) NMR experiments and were found to be 3.0, 2.5, and 3.4 nm, respectively. Keywords: carbohydrates; click chemistry; dendrimers; glycodendrimers; lectins; multivalent glycosystems; Introduction Multivalent

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• Scientifico e Tecnológico, 50019 Sesto Fiorentino, Firenze, Italy 10.3762/bjoc.10.156 Abstract Intermolecular interactions involving carbohydrates and their natural receptors play important roles in several biological processes. The development of synthetic receptors is very useful to study these recognition

• : conformational analysis; constant-pH MD; mannose; multivalent glycosystems; pH; synthetic receptor; Introduction The recognition of specific carbohydrates is an important step in several biological processes [1]. To better understand these recognition processes, several synthetic receptors have been developed

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• of compounds, the carbohydrates. Carbohydrates are involved in numerous biological recognition processes, where they are often displayed in the form of multivalent conjugates such as on the surface of cells [1]. To investigate multivalency in carbohydrate recognition, multivalent glycomimetics, for

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

• -carbohydrates, in particular multiarm PEGylation, is presented. Keywords: bioavailability; carbohydrates; conjugates; glycoPEGylation; multivalent glycosystems; multivalent PEGylation; Introduction In recent years, the modification of biotherapeutics by covalent conjugation with polyethyleneglycol (PEG) known

• recognized as immunodominant epitopes in antigenic glycoconjugates [14]. Carbohydrates participate in molecular recognition events such as host–pathogen interactions, responsible for mammal infections, and are candidates for chemotherapy [15]. Moreover, synthesis of multivalent carbohydrate ligands provide

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• Melanie Rauschenberg Eva-Corrina Fritz Christian Schulz Tobias Kaufmann Bart Jan Ravoo Organic Chemistry Institute, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany 10.3762/bjoc.10.138 Abstract The molecular recognition of carbohydrates and proteins mediates a

• wide range of physiological processes and the development of synthetic carbohydrate receptors (“synthetic lectins”) constitutes a key advance in biomedical technology. In this article we report a synthetic lectin that selectively binds to carbohydrates immobilized in a molecular monolayer. Inspired by

• microcontact printed on epoxide-terminated self-assembled monolayers. Successive prints resulted in simple microarrays of two carbohydrates. The selectivity of the synthetic lectin was investigated by incubation on the immobilized carbohydrates. Selective binding of the synthetic lectin to immobilized NANA and

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

• ]. Our methodology for preparing GNPs allows the construction of particles simultaneously containing carbohydrates, peptides and targeting molecules in a controled way [21]. The use of biocompatible gold glyconanoparticles as scaffolds for the antiviral drugs could bring some important benefits such as

• the improvement of the solubility in water and biological media of the drugs and the improvement of cellular uptake due to the presence of carbohydrates on the GNPs. In addition a local increase of the drug concentration on the gold surface could also improve their antiviral activity. We reasoned that

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• monovalent affinities of carbohydrate monosaccharides are comparatively low and weak. To enhance this multivalent effect, thereby increasing the binding efficiencies of carbohydrates with the coupling counterparts, there has been a constant development of new glycoconjugates such as glycodendrimers [57

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• -benzoate protected L-amicetose and a cinerulose derivative protected at C5 and C1. Keywords: carbohydrates; de novo synthesis; lactate; metathesis; ruthenium; Introduction Many drugs and bioactive natural products are glycoconjugates, which contain an aglycon part linked through glycosidic bonds to one

• for many years. For example, D-amicetose has been obtained from other carbohydrates through ethanethiolysis and subsequent Ni-catalyzed desulfurization [18][19], by reduction of the corresponding aldonolactone [20], or by conversion of a protected mannopyranoside into the 2,3-unsaturated enopyranoside

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

• third amino acid by carbohydrates presenting equidistant sugar units with uniform orientation in 5 Å intervals. Synthesized β-glycopeptides 1–8. ORTEP diagram of compound 10b. Preferential re-attack according to the Felkin–Anh model (TS 1) yielding 10b (left) and si-attack (TS 2) providing 10c (right

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• or ketones [23]. The most practical approach to a 2,4-disubstituted pyrrole reported to date is the recently disclosed microwave-assisted Stetter reaction of chalcone with carbohydrates as “green” formaldehyde equivalents followed by a microwave-assisted Paal–Knorr cyclization of the resulting 1,4

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• ; 1,2-oxazines; rearrangements; reductions; Introduction Since carbohydrates play a crucial role in biochemistry, compounds mimicking their structure and/or function (carbohydrate mimetics) have attracted great attention in academic research and in drug development [1][2][3]. These mimetics should not

• have the drawbacks of carbohydrates such as low binding affinity or instability [4][5]. Many carbohydrates and their mimetics contain pyran rings, however, the corresponding ring-expanded compounds, oxepanes, have been investigated only in a limited number of studies. Several oxepane units can be found