Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• improvements over the alternative active ester immobilization. Although not directly demonstrated in the current paper, our approach required considerably lower amounts of the inhibiting glycoconjugate in comparison to the reverse approach, which involves immobilization of lectin and titration of the binder

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• programmability of the assemblies lends itself to a combinatorial display of multiple ligands. Recent efforts in the synthesis and applications of such conjugates are discussed. Keywords: glycan; glycoconjugate; DNA display; multivalency; nucleic acid conjugates; oligomeric interaction; Introduction Cell

• spacers and capped by 3 different aryl groups (Figure 9). The fact that the library can be prepared by mix and split synthesis and reformatted in a spatially addressable microarray by simple hybridization [48] greatly facilitates access to diverse glycoconjugate arrays. Screening the library against a

• designed to emulate HIV's gp120 epitope. Combinatorial assembly and selection of two PNA glycoconjugate libraries on DNA templates. DNA display of ligand bridging opposing binding sites in a lectin (ECL). A glycan array prepared by hybridization of glycan–DNA conjugates and screening of RCA120. Multivalent

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• appropriate carbohydrate conjugation the same molecular architecture could be applied for organization of a divalent glycoconjugate (Figure 1B). We selected thymine as a photocontrollable element as it can undergo [2 + 2] photocycloaddition upon irradiation with light of hν ≥ 290 nm [5][9][10]. Furthermore

• used as scaffold molecule, and α-D-mannosides as specific carbohydrate ligands for the fabrication of the envisaged divalent glycoconjugate (Figure 1C). In the following, we report the synthesis of the divalent glycoconjugates outlined in Figure 1 and their [2 + 2] photocycloaddition. Results and

• of the targeted divalent thymine glycoconjugate started with the known 2-azidoethyl α-D-mannoside (1, Scheme 1) [11][12][13]. The kinetically controlled reaction of mannoside 1 with 2-methoxypropene delivers the 4,6-isopropylidene-protected derivative 2 in good yield, leaving the 2- and 3-hydroxy

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• reaction carried out with 1,2:3,4-di-O-diisopropylidene-α-D-galactopyranose yielded glycoconjugate 23 with an ether bond between the sugar and steroid molecules. In further studies on the preparation of glycoconjugates from 3β-hydroxy-Δ5-steroids, various derivatives were applied, such as thioethers [44

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• amounts of diene 13 and cholesteryl chloride (14) were also formed. In the reactions of i-cholesterol alkyl ethers (methyl 6b, ethyl, 6c, isopropyl 6d, and benzyl 6e), cholesterol glycoconjugate 11 was also formed in 40%, 51%, 41%, and 50% yield, respectively. Glycoconjugate 11 was accompanied by

• substantial amounts of isomerization products 12 (24–45%) and tiny amounts of other products (cholesterol (1), dicholesteryl ether (2), diene 13, and cholesteryl chloride 14). The best yield (58%) of cholesterol glycoconjugate 11 was achieved with 3α,5α-cyclocholestan-6β-yl phenyl ether (6f). The reaction was

• fact that cholesteryl phenyl thioether proved to be a rather poor cholesteryl donor for the electrochemical reaction (12% yield). In contrast to the above, the reaction of 4-hydroxyphenyl i-cholesteryl ether 6g was messy and afforded only 9% of the desired glycoconjugate 11. The isomerization product

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

• epitopes. Use of tetanus toxoid (TTox) and bovine serum albumin (BSA) as immunogenic carrier proteins allows application of these conjugates in immunization studies and diagnostic ELISA experiments [44]. Results and Discussion Chemical synthesis of the 4’-fluoro-TF neo-glycoconjugate The synthesis of the 4

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 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

• Markus Norrlinger Thomas Ziegler Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany 10.3762/bjoc.10.256 Abstract New aromatic glycoconjugate building blocks based on the trifunctional 3-aminomethyl-5-aminobenzoic acid backbone and sugars

• combinatorial glycopeptide libraries which will be screened for their capability to bind to specific proteins [5][6][7][8][9][10][11]. Those results will be published elsewhere. Malonyl-linked aromatic glycoconjugate building blocks for spot synthesis of combinatorial glycopeptides libraries. Synthesis of the

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

• diphtheria toxin Cross-Reacting Material 197 (CRM197), a protein widely used in manufactured vaccines,[17] provides a potent candidate for the development of a glycoconjugate vaccine against this serogroup [18]. MenX CPS is a homopolymer of (1→4)-linked 2-acetamido-2-deoxy-α-D-glucopyranosyl phosphate

• 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

• another key parameter which has been shown to deeply affect the immunogenicity of glycoconjugate vaccines [42][43]. In the present preliminary study, glycoconjugates with moderate loading were compared. It has been reported for other bacterial systems that the immunogenicity of short oligosaccharides can

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• glycocluster ligands per monomer of lectin. The trivalent tris-galacosylated glycoconjugate 1 displays a good affinity and a Kd value of 1.09 µM, compared to 94 µM for the monovalent reference, methyl β-D-galactoside (Table 1). The stoichiometry indicates that each cluster binds to three lecA sites. The tris

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

• ). Due to the partial hydrophobic nature of the dendrons 1–3 they do not fully dissolve in the buffer, and the solution is not completely clear. The dendrons 1–3 were reacted overnight at room temperature with α-O-L-fucopyranosyloxyamine (5) affording the desired glycoconjugate structures 7, 9 and 11 in

Bis(β-lactosyl)-[60]fullerene as novel class of glycolipids useful for the detection and the decontamination of biological toxins of the Ricinus communis family

• Hirofumi Dohi,
• Takeru Kanazawa,
• Akihiro Saito,
• Keita Sato,
• Hirotaka Uzawa,
• Yasuo Seto and
• Yoshihiro Nishida

Beilstein J. Org. Chem. 2014, 10, 1504–1512, doi:10.3762/bjoc.10.155

• , Tsukuba, 305-8565, Japan 10.3762/bjoc.10.155 Abstract Glycosyl-[60]fullerenes were first used as decontaminants against ricin, a lactose recognition proteotoxin in the Ricinus communis family. A fullerene glycoconjugate carrying two lactose units was synthesized by a [3 + 2] cycloaddition reaction

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

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

• glycoconjugate to a scaffold or surface, respectively, after suitable postsynthetic modification at the focal point of the molecule. Moreover, such an approach opens the door to a number of intriguing applications of multivalent glycoconjugates such as incorporation into a supramolecular assembly, for example

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

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

• Paola Bonaccorsi,
• Maria Luisa Di Gioia,
• Antonella Leggio,
• Lucio Minuti,
• Teresa Papalia,
• Carlo Siciliano,
• Andrea Temperini and
• Anna Barattucci

Beilstein J. Org. Chem. 2013, 9, 2410–2416, doi:10.3762/bjoc.9.278

• higher binding affinities owing to the sum of the individual interactions [5]. The synthesis of sugar-decorated molecular systems represents a significant tool in glycobiology and glycomic research fields [6]. The general prototype of a glycoconjugate comprises a core molecule that serves as an

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

• virulence property of the pathogen, several reports appeared in the past on the development of glycoconjugate based therapeutics against bacterial infections [10][11][12]. Detailed biological studies of the glycoconjugates require a significant quantity of the oligosaccharides, which is difficult to isolate

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

• therapeutics against this organism. Since, bacterial cell-wall lipopolysaccharides play important roles in the pathogenicity of the virulent strains, it would be pertinent to develop glycoconjugate therapeutics based on the cell-wall oligosaccharide haptens to reduce the number of infections [9][10][11][12

• ]. In order to evaluate the therapeutic efficacy of the glycoconjugate derivatives it is essential to have a significant quantity of oligosaccharides, which is difficult to isolate from natural sources. Therefore, the development of a chemical synthetic strategy for the synthesis of the oligosaccharides

• and their close analogues can add momentum towards the preparation of glycoconjugate-based therapeutics. In this perspective, we report herein a concise chemical synthesis of the tetrasaccharide repeating unit of the cell-wall lipopolysaccharide of E. coli O40, using a convergent block synthetic

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

• trisaccharide [16][17][18][19][20][21]. The relative affinity of the anti-Lex monoclonal antibody SH1 [6] for the native Lex antigen 1 and our Lex analogues [12][13][14] was examined by competitive ELISA experiments using a Lex-BSA glycoconjugate as the immobilized ligand [15][22][23][24]. It was discovered

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

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

• minimal human interference [41], making the update of these data much less dependent of funding than that of data extracted from the literature. Carbohydrate data from the PDB are also available in the Glycoconjugate Database [26], but updates are less frequent than in Glycosciences.DB, which is updated

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

• Tatiana V. Kulakovskaya Ekaterina V. Kulakovskaya Nikolay E. Nifantiev Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow, Russian Federation Laboratory of NMR spectroscopy, N. D. Zelinsky Institute of

• temperature (22 ± 2 °С) and humidity under a 12/12 h light/dark cycle. All the procedures were carried out in strict accordance with the International Legislation on the Use and Care of Laboratory Animals. Glycoconjugate vaccine preparation: Conjugate (3’SL-KLH [28]) of α-NeuAc-(2→3)-β-Galp-(1→4)-β-Glcp

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

• coupling of a deprotected poly-LacNAc–linker–NH2 glycan (17), which was synthesised as described previously [45][55]. On an analytical scale, a heptasaccharide–linker–NH2 glycoconjugate 17 was coupled to the aldehyde groups of 3a or 10a by reductive amination leading to the chemically branched poly-LacNAc

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

Synthesis in the glycosciences II

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2012, 8, 411–412, doi:10.3762/bjoc.8.45

• certainly one of the most exciting and promising divisions of modern chemistry. The many different works contributed to this Thematic Series impressively demonstrate the variety in the glycosciences. Fantasy and imagination have led to novel glycoconjugate architectures and glycobiological experiments

• . Expertise and rational planning have allowed the utilization of carbohydrates in stereoselective synthesis and the employment of enzymes in oligosaccharide synthesis. Analytical and pharmacological knowhow have disclosed polysaccharide and glycoconjugate structures, their biological effects and their

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

• earlier to develop glycoconjugate based therapy to control Shigella infections [15][16][17][18][19]. In order to develop a glycoconjugate based therapeutic agent from the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9, it is essential to perform several immunochemical studies

• group under phase transfer conditions without affecting the secondary hydroxy groups; (c) use of 4-methoxyphenyl (PMP) group as anomeric protecting group [30][31], which can be easily removed under oxidative conditions for the preparation of glycoconjugate derivatives. The synthesis of the target