Low-generation dendrimers with a calixarene core and based on a chiral C₂-symmetric pyrrolidine as iminosugar mimics

• Marco Marradi,
• Stefano Cicchi,
• Francesco Sansone,
• Alessandro Casnati and
• Andrea Goti

Beilstein J. Org. Chem. 2012, 8, 951–957, doi:10.3762/bjoc.8.107

• occasionally, and their properties as multivalent enzyme inhibitors gave contrasting results. Early findings indicated in fact that poor multivalent phenomena take place [4][5][6], but more recently moderate [7] to remarkable [8][9] effects have been reported on glycosidases. Unlike lectin-mediated

• enhance the avidity of interactions between glycans and lectins [15]. Some glycocalixarenes have shown remarkable inhibition properties towards galectins [21][22] or Pseudomonas Aeruginosa lectin [23], the inhibition ability being dependent on the macrocyclic conformation and presentation of the glycoside

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

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

• proteins (GBPs) or lectins is stored in various databases such as CFG GBP DB, GlycoEpitopeDB [54], the Glycan Binding Proteins section of KEGG BRITE, Lectin Frontier Database, and GlyAffinity. KEGG BRITE mainly links to other resources within and outside the KEGG portal, providing protein sequences

• arrays [4]. CFG Glycan Binding Proteins DB and Lectin Frontier Database store data of glycan array experiments and thus also provide information on the glycan specificity of GBPs. Glycan array data from these two resources and from other research groups are collected and available via a common interface

• , however, can be difficult when using PDB queries only. Instead, glycan databases that provide links to PDB entries such as GlycoconjugateDB or Glycosciences.DB can be used. The LECTINES database lists PDB entries of lectins grouped by lectin families. Unfortunately, carbohydrate moieties in the PDB are of

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• conveniently prepared by employing a one-pot procedure for Cu(II)-catalyzed diazo transfer and Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) starting from commercially available amines. These glycoclusters were probed for their binding potencies to the plant lectin wheat germ agglutinin (WGA) from

• Triticum vulgaris by an enzyme-linked lectin assay (ELLA) employing covalently immobilized N-acetylglucosamine (GlcNAc) as a reference ligand. IC50 values were in the low micromolar/high nanomolar range, depending on the linker between the two disaccharides. Binding enhancements β up to 1000 for the

• receptor–ligand interactions is the multivalent presentation of sugar epitopes on suitable scaffolds. This principle is not only used in nature but is also a valid strategy for the construction of artificial lectin ligands [3][4][5][6][7][8][9][10][11][12][13]. Prime examples are the recently described

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

• and lectin binding [95][96][97][98][99][100][101][102][103][104][105]. The synthesis of glycoclusters/dendrimers is an area of research aimed at tackling the increasing problems with bacterial multi-antibiotic resistance. Microbe adherence to the glycans on the tissue cell surface is essential for an

• microbe and lectin binding studies, glycopeptide based glycoclusters/dendrimers were applied, employing linear peptide backbones, cyclic peptide scaffolds or multi-lysine scaffolds [106][107][108][109][110][111][112][113][114][115][116][117][118]. The pentavalent cholera toxin protein secreted by Vibrio

• cholerae, causes severe diarrhea and massive dehydration upon binding and entrance into the intestinal epithelial cells [119]. The AB5-type toxin consists of one toxic ADP-ribosyltransferase and five lectin subunits that bind to the gangloside GM1 ligands on the epithelial cell surface [120]. The cholera

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

• binding to lectin-like domains on fibronectin. The negatively charged sulfate group could also block cell–ECM interactions by interfering with heparin binding sites on fibronectin [21] and fibrinogen [22], which recognize the sulfated groups of cell-surface-expressed GAGs. GSF could mimic the highly

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

• generally confirmed indirectly by lectin binding, which severely limits the ligands that can be interrogated to those that can be detected by carbohydrate-binding proteins. To overcome this limitation, we were interested in developing label-free methods for ligand detection on these polystyrene surfaces

• be useful in a bacterial adhesion inhibition assay against the bacterial lectin FimH [20][21]. The second glycoside 7 has been used previously for well-established enzymatic surface modifications [22]. Both these compounds can be synthesised by starting from commercially available 11

• 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

• -containing glycans trigger the cellular immune response of natural killer cells [10][11][12]. Scientific interest in the synthesis of naturally occurring and modified LacNAc and poly-LacNAc glycans is high, as they can be used for the detailed investigation of lectin binding modes and their biological

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

• acids at randomized positions on a topological cyclopeptide scaffold [26]. Deconvolution of the resulting libraries by affinity chromatography allowed the selection of heteroglycoclusters that were proved to be useful for exploring the surrounding regions of the binding pocket in a model lectin

• 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

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• biosynthesis of N-linked glycoproteins: Glc(α1→3)Glc and Glc(α1→3)Man. The Alt(N2–6)Man structure does not bear an immediately obvious resemblance to either of these substructures. Moreover, it has been proposed that a mannose-binding lectin domain of the α-glucosidase II β-subunit is also important for its

• activity [50], and the possibility that the inhibitor is actually binding not to the enzyme active site, but to this lectin domain instead, is not ruled out at present. Conclusion Unsaturated carbohydrate derived electrophiles react readily with carbohydrate nitrogen nucleophiles to form amine-linked

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• , following immobilization on glass slides, their binding to the lectin DC-SIGN was assessed [31]. Significant questions remain in the area of PIM/LM/LAM biosynthesis that could be assisted by suitable well-defined mannan substructures. For example, the identity of the α-1,2-mannosyltransferase(s) involved in

• solubility relative to other common alternatives, and ability to be excited using visible, rather than ultraviolet light [44]. Hindsgaul and coworkers have reported the use of glycoconjugates with NBD dyes to streamline the detection of carbohydrate-lectin interactions and report that the NBD group displayed

En route to photoaffinity labeling of the bacterial lectin FimH

• Thisbe K. Lindhorst,
• Michaela Märten,
• Andreas Fuchs and
• Stefan D. Knight

Beilstein J. Org. Chem. 2010, 6, 810–822, doi:10.3762/bjoc.6.91

• , Uppsala Biomedical Center, SE-75124 Uppsala, Sweden 10.3762/bjoc.6.91 Abstract Mannose-specific adhesion of Escherichia coli bacteria to cell surfaces, the cause of various infections, is mediated by a fimbrial lectin, called FimH. X-ray studies have revealed a carbohydrate recognition domain (CRD) on

• FimH that can complex α-D-mannosides. However, as the precise nature of the ligand–receptor interactions in mannose-specific adhesion is not yet fully understood, it is of interest to identify carbohydrate recognition domains on the fimbrial lectin also in solution. Photoaffinity labeling serves as an

• ) [1]. It has become our goal to utilize this methodology for the investigation of carbohydrate binding of the bacterial lectin FimH. The protein FimH is found on the tips of type 1 fimbriae, long adhesive filamentous appendages on the surface of many bacteria, such as Escherichia coli [2][3][4][5]. In

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

• Thisbe K. Lindhorst Kathrin Bruegge Andreas Fuchs Oliver Sperling Christiana Albertina University of Kiel, Otto Diels Institute of Organic Chemistry, Otto-Hahn-Platz 4, D-24098 Kiel, Germany, Fax: +49 431 8807410 10.3762/bjoc.6.90 Abstract FimH is a mannose-specific bacterial lectin found on type

• dispersed throughout the lectin domain are a possible explanation for this finding. This feature could aid in recognising large and multivalent carbohydrate receptors respectively, on the host surface. In order to look for possible additional carbohydrate-binding sites in the FimH lectin, the surface of the

• lectin domain was probed by computational docking studies [16]. Three new potential carbohydrate binding cavities on the surface of the FimH lectin domain, in addition to the mannose pocket at the tip of the domain, were identified which have a marked preference for the same subset of high-mannose

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• Pluronic® F-68. The mannose moieties are accessible at the surface of nanoparticles and available for molecular recognition by concanavalin A lectin. Interaction of mannose units with the lectin were evaluated by measuring the changes in nanoparticles size by dynamic light scattering in dilute media

• . Keywords: click chemistry; con A lectin; dynamic light scattering; glycopolymer; polymer nanoparticles; Introduction Over the last decades, research efforts in pharmaceutical, food and cosmetics technologies have been directed not only towards the syntheses of new bioactive entities or medicines, but also

• surfactants for mini-emulsion polymerization [5][6]. Amphiphilic block copolymers with pendant glucosamine units have been obtained by living cationic polymerization and their interaction with wheat germ agglutinin lectin investigated [7]. More recently, the synthesis of neoglycopolymers by living radical

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• cells has been demonstrated [3][7]. The sialic acid modifications influence the interaction with sialic acid binding immunoglobulin-like lectin (Siglec)-2 and infection processes of BJA-B cells by the B-lymphotrophic papovavirus [8]. It was further shown that the uptake and incorporation of alkynylated