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

• changes in glycosyltransferase activity and expression [8][9][10]. Furthermore, the prevalence of truncated saccharide antigens such as the Tn antigen [11], the Thomsen–Friedenreich (TF) antigen, and their sialylated congeners [8][9][10][12] leads to an insufficient shielding of the peptide backbone

• glycoengineering, the structural integrity of the saccharide epitope must be maintained and cross-reactivity of the elicited antibodies with the native tumor-associated glycans is required. In this respect, the use of fluorinated TACAs [28][39][40][41][42] is a promising strategy due to the ability of C–F moieties

• capable of binding to the native MUC1 antigen structures present on MCF-7 human breast cancer cells. Moreover, selective deoxyfluorination at the antigenic carbohydrate determinant might be used to improve the metabolic stability of the saccharide epitope, as was showcased by the enhanced resistance of

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase) and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS) to build

• conjugates of saccharide–amino acids–nucleobase (SAN), like the previously reported conjugates of nucleobase–amino acids–saccharide (NAS) and nucleobase–saccharide–amino acids (NSA), are mammalian cell compatible. Keywords: cell compatibility; nucleobase; peptides; saccharide; Introduction As a result of

• types of building blocks for generating supramolecular nanofibers in water [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Recently, we have demonstrated that not only the conjugates of nucleobase–amino acids–saccharide (NAS) [16][17][18] but also the conjugates of nucleobase–saccharide–amino acids

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

• latter analytical technique enabled determination of the saccharide/protein molar ratio (saccharide loading). The characteristics of the prepared glycoconjugates are summarized in Table 1. A moderate loading (5–7 sugars/protein) was obtained in compounds 14–16 in respect to conjugates prepared by the

• . Immunological evaluation of CRM197 conjugates To evaluate the immunogenicity of the synthesized glycoconjugates, groups of 8 BALB/c mice were immunized with three doses (two weeks apart) of 0.3 μg on saccharide base of the neo-glycoconjugates. The conjugated trimer 16 was also injected at 1 μg carbohydrate base

• (MenXDP15-CRM conjugate, compound 17) was used at the saccharide base doses of 0.3 and 1 μg, respectively. As shown in Figure 2, while the CRM197 conjugates of the monomer 1 and the dimer 2 did not induce polysaccharide specific IgG titers, the conjugated trimer 3 elicited anti-MenX CPS IgG titers, with no

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

• simple alkyl or aryl branched-chain sugars involves the addition of Grignard reagents. In this regard, a wide variety of Grignard reagents have been added to the free or masked (as hemiacetal) carbonyl functionalities present in the molecule of a suitable fully O-protected saccharide, thereby making

• relative ratio of o-tolyl and benzyl isomers. Finally, for the separation of o-tolyl isomer from benzyl isomer, a mixture of all four chromatographically non-separable isomeric alcohols 4–7 was oxidised using PDC, thereby destroying the chiral center at C-5 position of the saccharide moiety, to afford a

• unambiguously confirmed by single-crystal X-ray analysis. The formation of o-tolyl isomers 4 and 5 can be explained by the possible reaction sequence (path 1) depicted in Scheme 2. The first step involves an addition of the Grignard reagent to the saccharide aldehyde, producing a trienic magnesium alkoxide

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

• quantitative yields. Conclusion In conclusion, novel G0, G1 and G2 dendrons suitable for glycoconjugation by carbonyl chemistry were synthesized. The conjugation of the saccharide by reductive amination was characterized by a low efficiency. On the other hand, the oxime ligation afforded the glycoconjugated

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

• Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy 10.3762/bjoc.10.175 Abstract Four novel calix[4]arene-based glycoclusters were synthesized by conjugating the saccharide units to the macrocyclic scaffold using the CuAAC reaction and using long and hydrophilic ethylene glycol spacers

• . Initially, two galactosylcalix[4]arenes were prepared starting from saccharide units and calixarene cores which differ in the relative dispositions of the alkyne and azido groups. Once the most convenient synthetic pathway was selected, two further lactosylcalix[4]arenes were obtained, one in the cone, the

• ] saccharides. Usually, either the strategy of reacting an alkynylated-saccharide with a polyazide calixarene (dipolarophile-on-the-sugar) or an azido-sugar and a polyalkynocalixarene (dipolarophile-on-the-calix) work smoothly [33]. However, a sort of autocatalytic effect was evidenced in the case of the

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

• -peptide incorporation of sugar-β-amino acids are described providing the saccharide units as amino acid side chain. The respective sugar-β-amino acids are accessible by Michael addition of ammonia to sugar units derivatized as α,β-unsaturated esters. Three sugar units were incorporated in β-peptide

• peptide scaffolds for the presentation of sugar epitopes has already some precedence. Complex saccharide structures are linked to α-peptides, protein fragments [24][25][26][27] and recently also to glycofoldamers [28]. Sugars are arranged on cyclopeptides [29][30][31][32][33], like Dumy and coworkers

Gold-catalyzed glycosidation for the synthesis of trisaccharides by applying the armed–disarmed strategy

• Abhijeet K. Kayastha and
• Srinivas Hotha

Beilstein J. Org. Chem. 2013, 9, 2147–2155, doi:10.3762/bjoc.9.252

• carbohydrate chemistry was first reported for the oxidation of alcohols [11][12][13][14][15][16]. However, until recently these catalysts were scarcely applied. Glycosidation is one of the key reactions in chemistry of carbohydrates, in which a nucleophile attaches to a saccharide to form a glycoside. In this

• process, the saccharide unit that is donating its glycon is called a glycosyl donor, whereas the saccharide that is accepting the glycon is referred to as glycosyl acceptor or aglycon. The synthesis of oligosaccharides is still a formidable task in spite of the development of various methods. There is

• ][32][33][34]. Esters at the C-2 position of the saccharide are known to impede the glycoside formation whereas ethers (–OBn) facilitate the reaction. Fraser-Reid applied the terms disarmed to deactivated glycosyl donors [e.g., esters], and armed to the activated donors [e.g., ethers] [35][36]. During

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

• though is widely accepted that mucins form a protective layer over the epithelium, the mechanisms to achieve this are poorly understood [4][5]. A characteristic feature of all mucins is the linking region of the protein backbone with the saccharide side-chain, which is typically an α-linked 2-acetamido-2

• -deoxy-D-galactose to serine or threonine. This saccharide forms the inner part of the characteristic core oligosaccharides from where glycans are extended through common core (di- and trisaccharide) structures, cores 1–8 [6][7][8]. The mucin-type oligosaccharides identified to date have remarkable

• building blocks containing leaving groups with orthogonal reactivities that can be activated independently. Saccharide building blocks can then be assembled without the need for additional protecting-group manipulations between glycosylations and the coupling sequence can be performed with glycosyl donors

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

• malignancy is well described for melanomas [4]. It is also a prerequisite for the activation of pro-MMP-2, a secreted metalloprotease important for cell migration through the basal layer [5]. Due to the vast variability of branched saccharide chains, more specific interactions between cells and the ECM and

• oligosaccharides and lectins, by synthetic carbohydrate analogues [10][11][12][13]. Based on Schmidt’s imidate strategy [14], we have developed a method for the synthesis of a library of saccharide-mimetics containing furans. Furan, especially as its bis-hydroxymethylated derivative, was chosen as a core molecule

• of the carbohydrate moieties unaffected [15]. With biotin-labeled Diels–Alder products of branched saccharide mimetics, discrete staining patterns were observed on surfaces of human epithelial tumor cells, but not on immortalized normal fibroblasts. Screening of the library to find members with anti

Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS

• Martin J. Weissenborn,
• Johannes W. Wehner,
• Christopher J. Gray,
• Robert Šardzík,
• Claire E. Eyers,
• Thisbe K. Lindhorst and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 753–762, doi:10.3762/bjoc.8.86

• the direct analysis of any noncovalent glycoarray on glass and polystyrene. So far, our attempts to study enzymatic reactions on the modified polystyrene surface have been unsuccessful and will require further investigation. Experimental General experimental section for the saccharide synthesis

• applied to the surface and the solvent was allowed to evaporate under atmospheric conditions. Unless otherwise stated, the spots were washed by following procedure 1. Carbohydrate arrays on polystyrene slides can be obtained by noncovalent immobilisation of tritylated saccharide derivatives. (A) Lectin

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

• 7a and 7b was proven by the presence of a C4–C5 double bond in the terminal saccharide unit. For compounds 15a and 15b the HSQC-TOCSY experiment was fundamental for the assignment of particular proton spin systems of individual saccharide units, the –N(CH2)2N– and –(CH2)5N– groups of spacers, and the

• spin system –(CH2)4CHCH(N–)CH(N–)CH2– of biotin. The anomeric configuration (β) of all saccharide units was determined from the JH-1,H-2 coupling constants. Chemical shifts of GlcNAc carbons C-2 agree with N-acetylation. Because of isomerism on the NH–C=S bond, protons H-1A resonate as two broad

• transfer, and the reaction mixtures were incubated at 30 °C under gentle mixing at 60 rpm for 5.5 h. For the oxidation of 10 µmol t-Boc-saccharide (1a–d, 2), 15.5 U galactose oxidase and 322 U peroxidase were used. Samples were taken to control the progress of the synthesis and the reactions were stopped

Acceptor-influenced and donor-tuned base-promoted glycosylation

• Stephan Boettcher,
• Martin Matwiejuk and
• Joachim Thiem

Beilstein J. Org. Chem. 2012, 8, 413–420, doi:10.3762/bjoc.8.46

• ; however, regioselective and stereoselective glycosylations remain difficult and alternative concepts are welcome, and should be considered and studied. Recently regioselective and β-stereospecific glycosylations employing saccharide oxyanions have been presented. Initial studies on base-promoted

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• intramolecular, ring-closing condensation occurs affording a tethered saccharide (Figure 1). Despite the fact that the “prearranged-glycoside concept” for intramolecular glycosylation has been successfully applied to the construction of glycosidic bonds that are otherwise difficult to establish (i.e., β-D

• , depends on the peptide tether (peptide-templated saccharide synthesis) [41][42]. Therefore, in order to understand these factors better, we performed a molecular modeling study for the intramolecular glycosylation of the prearranged glycosides 5 and their cyclization products 6–8. Molecular modeling

Symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems

• Sławomir Boncel,
• Maciej Mączka,
• Krzysztof K. K. Koziol,
• Radosław Motyka and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2010, 6, No. 34, doi:10.3762/bjoc.6.34

• unreactive towards the carboxylic group when compared to the amine functionality, and consequently nucleosides with a saccharide moiety (23, 25) were successfully synthesised. Self-assembly of aliphatic long-chain symmetrical α,ω-nucleobase amide-conjugated systems For the microscopic studies, we selected

Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• . Today, 30 years after the first reports on carbohydrate-based ligands [1][2][3][4], the potential of saccharide compounds in this area is more and more appreciated [5][6][7][8][9][10][11][12]. Chiral bis(oxazolines) (Box) are very efficient ligands for many asymmetric transformations [13][14]. Even

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• ′ terminus with (1→6)-amide-linked oligosaccharide mimics (Figure 9). The presence of the saccharide unit at the 3′-end of 18-mers significantly enhanced the stability of the oligonucleotides in bovine fetal serum, non-negatively interfering with their ability to form stable duplexes with complementary DNA

• interest because these functional groups are isosteric with phosphodiesther groups occurring in oligoglycosylphosphates and nucleotides. Some examples of natural compounds having saccharide units connected by pseudoamide linkage are known. For example, the family of glycocinnamoylspermidine antibiotics 26

• alternating α,α-trehalose motifs and semi-rigid thiourea segments (cyclotrehalans, CTs) [77][78][79][88][89]. Molecular diversity was introduced at the inter-saccharide connectors by exploiting the chemistry of macrocyclic carbodiimides [77][78][79][88][89] as well as by varying the size of the macrocycle

Chemical synthesis using enzymatically generated building units for construction of the human milk pentasaccharides sialyllacto-N-tetraose and sialyllacto-N-neotetraose epimer

• Dirk Schmidt and
• Joachim Thiem

Beilstein J. Org. Chem. 2010, 6, No. 18, doi:10.3762/bjoc.6.18

• of enzymatic and purely chemical procedures was shown to be advantageous in the preparation of complex oligosaccharides. Experimental For general methods cf. reference [16]. The NMR data for the saccharide rings in the pentasaccharides 7, 8, 13 and 14 are denoted according to the Roman numberals I-V

• (16s, 48 H, 14 OAc, 2 NAc), 2.01 (dd, J3ax,4 = 12.0 Hz, 1 H, H-3axV), 1.00 (s, 9 H, SiCCH3). C69H96N2O44 (1657.49): Found C, 49.86; H, 5.77; N, 1.65. Calculated C, 50.00; H, 5.84; N, 1.69. MALDI-TOF: 1680.39 (M+Na)+; 1696.59(M+K)+. Structures of pentasaccharides 1 and 2. Roman numbering of saccharide

Recognition properties of receptors consisting of imidazole and indole recognition units towards carbohydrates

• Monika Mazik and
• André Hartmann

Beilstein J. Org. Chem. 2010, 6, No. 9, doi:10.3762/bjoc.6.9

• carbohydrate-based molecular recognition processes and might serve as a basis for the development of new therapeutic agents (for example, anti-infective agents) or saccharide sensors [19][20][21][22][23][24][25][26]. Our previous studies showed that mimicking the binding motifs observed in the crystal