Glycodendrimers: tools to explore multivalent galectin-1 interactions

• Jonathan M. Cousin and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2015, 11, 739–747, doi:10.3762/bjoc.11.84

• multivalent ligands displaying multiple copies of recognition elements are a logical tool to study mechanisms of galectin-1 mediated biological activities. Mutivalent frameworks have been used to organize lectins and to mediate biological activity for the advancement of mechanistic understandings [22][23][24

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

• single high-affinity interaction with a target macromolecule, glycans’ interactions with glycan-binding proteins (GPB) or lectins are typically low affinity. However high avidity and specificity is achieved through the concerted interactions of multiple ligands with well-defined spatial geometry [5]. The

• for hybridization to DNA arrays and screened against lectins from pathogenic P. aeruginosa (PA2L and LecA) [51][52][53]. Our group used DNA microarrays to combinatorial pair diverse PNA-tagged glycan conjugates displayed at adjacent hybridization sites to produce assemblies emulating the diversity of

• di-, tri- and tetra-antennary glycans (Figure 8) [39]. Using two sets of 25 PNA conjugates, an array of 625 unique assemblies was produced. Importantly, screening different lectins (ConA or peanut lectin) indicate a synergy between the paired fragments with a composition consistent with the known

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

• influence their recognition by lectins [7]. Recently, we have introduced a photoswitchable glycoazobenzene-covered surface, in which alteration of ligand orientation allowed to switch cell adhesion without changing the recognition quality or the valency of the ligand itself [6]. It is also well-known that

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• as selectin inhibitors. There we have found that sulfated aminopyrans connected by amide bonds to gold nanoparticles are highly potent inhibitors of L- and P-selectin with IC50 values in the subnanomolar range [12][13]. These lectins are crucial in the inflammatory process [14][15][16][17][18] and

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

• were used for combinatorial solid phase or automated spot synthesis of libraries of highly glycosylated peptides and shown to specifically bind to lectins [5][8][10]. Here, we now describe the preparation of a series of glycopeptide building blocks which allow for the construction of glycopeptide

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

• target for pharmacological intervention. Further investigations of the specific functions played by these lectins in PA biofilm formation will provide useful understanding, and ultimately a means of prevention of PA virulence. The creative design of glycomimetics that can interfere or can modulate the

• bioactivity of these lectins in host recognition and adhesion in biofilm formation represents an attractive antibacterial strategy, as multivalent carbohydrate motifs on cell surfaces are known to mediate a broad range of cellular and tissue adhesion processes. Carbohydrate recognition in biological systems

• lectins in the form of glycoclusters [17], poly(glycomer)s [18][19][20][21], and glycodendrimers [22][23][24]. In regards to PA, C-fucosylpeptide dendrimers were shown to inhibit biofilm formation and to efficiently disperse established biofilms in both reference and hospital strains of PA [25][26][27

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

• plasmon resonance; Introduction Lectins are carbohydrate-binding proteins (CBP) [1][2][3] without any catalytic or immunogenic activity. In the latest decades, they attracted an increasing interest due to their involvement in a series of fundamental biological processes such as cell adhesion, cell

• activation, cell growth, differentiation and apoptosis. Among different families of lectins, the ones showing a selectivity for β-D-galactoside and β-D-galactose-terminating oligosaccharides are called galectins and play important roles in a series of pathological events such as inflammation, fibrosis, heart

• efficient multivalent ligands for a series of pathological lectins. For instance, cholera toxin is bound rather efficiently by calix[4]arene [16] and calix[5]arene [17] derivatives, while examples of Pseudomonas aeruginosa LecB binding were reported with galactosylcalixarenes blocked in different

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

• highly interesting to also modulate the binding affinity of a single molecule through a structural change as a response to an external stimulus, for example light. In order to gain such control over the binding affinity of glycooligomers towards specific lectins, a few studies have recently been

• affinity towards PA-IL lectins on demand, we were intrigued in the ability of our light-responsive systems to work when immobilized on a surface. To this end we attached the photoswitchable precision glycooligomers directly to the SPR chip and performed a second set of lectin binding experiments using SPR

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

• indicated that the glycoprotein ligand could serve to initiate aggregation, but carbohydrate binding was not required for all of the galectin-3 lectins that were involved in the interaction. Some galectin-3/galectin-3 interactions, in addition to carbohydrate/galectin-3 interactions, were proposed [18]. A

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

• experimental conditions that often biased the intrinsic phenomena under investigations [29]. For instance, when evaluating thermodynamic parameters by isothermal calorimetry (ITC), scientists used either truncated versions of for instance, tetrameric lectins such as ConA, or diluted conditions to avoid

• kinetic abilities towards multivalent lectins, we designed three families of closely related mannopyranoside dendrimers. Scheme 1 describes the preparation of trimers 5 and 9 built around benzene-1,3,5-tricarboxamide (BTA or trimesamide core) having respectively nine and ten atoms between the anomeric and

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

• ; ricin; Introduction Carbohydrate-binding proteins (lectins) and proteotoxins, e.g., verotoxins [1][2] and cholera toxins [3], can cause serious damages to human cells. The carbohydrate binding proteins are able to interact with cell-surface glycoconjugates such as glycoproteins and glycolipids to

Multichromophoric sugar for fluorescence photoswitching

• Stéphane Maisonneuve,
• Rémi Métivier,
• Pei Yu,
• Keitaro Nakatani and
• Juan Xie

Beilstein J. Org. Chem. 2014, 10, 1471–1481, doi:10.3762/bjoc.10.151

• -functionalized moieties [18][19][20]. Monosaccharides can be readily functionalized with several propargyl groups to synthesize, using click chemistry, multivalent neoglycoconjugates for recognition studies with carbohydrate-binding proteins (lectins) [21][22][23][24] or to develop light-harvesting antenna

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

• units of mannose, fucose or lactose, have been incorporated into the surface of PEGylated dendritic polymers by means of click chemistry. The larger dendrimer generations have demonstrated an increased capacity to aggregate lectins [47]. Analogs of lactose have been reported as inhibitors of the enzyme

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

• 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

• β-D-galactose was observed by fluorescence microscopy. The selectivity and affinity of the synthetic lectin was screened in competition experiments. In addition, the carbohydrate binding of the synthetic lectin was compared with the carbohydrate binding of the lectins concanavalin A and peanut

• agglutinin. It was found that the printed carbohydrates retain their characteristic selectivity towards the synthetic and natural lectins and that the recognition of synthetic and natural lectins is strictly orthogonal. Keywords: carbohydrates; lectins; molecular recognition; microarrays; multivalent

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

• corresponding lectins. Taillefumier and coworkers link sugar units to β-peptide amino acid side chains by azide–alkyne cycloaddition [20]. Following the concept of highly organized presentation of sugar units on a β-peptide scaffold, we report on simultaneous incorporation of various sugars (glucose, galactose

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

• oligovalent scaffold, a number of sugar moieties, and suitable spacers which link the sugar moieties to the central core. Several examples of such molecular architectures have been obtained, and it has been demonstrated that these compounds are well-suited for the binding of lectins because of the glycoside

Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• attach to certain carbohydrate ligands of a glycosylated surface such as the glycocalyx of eukaryotic target cells (Figure 1A) [1][2][3][4]. This offers the possibility to inhibit bacterial adhesion by designed antagonists of the respective carbohydrate-specific bacterial lectins [5]. In order to expand

• the scope of carbohydrate-based antiadhesives, it has become our goal to make photoswitchable ligands of bacterial lectins to allow blocking of bacterial adhesion in a photocontrolled manner. One of the best-known fimbriae are the type 1 fimbriae of uropathogenic E. coli (UPEC), which comprise the α-D

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• its flexible divalent counterpart. There are no other examples in the literature that show inhibition studies of lectins using divalent ligands directly connected by a rigid spacer based on phenylene-ethynylene units (Figure 1b). In order to systematically study the effects of spacer lengths on the

• hydrophilic than simple sugars. We have been developing pseudo-disaccharide molecules such as 23 [32] (Scheme 7) as mimics of mannose disaccharides for the interaction with DC-SIGN and other C-lectins [33][34][35]. This molecule and its derivatives [36] contain lipophilic moieties that generally increase

• polyvalent glycomimetics with regularly spaced cores to be used for Man-specific C-lectin inhibition assays. With access to structural data of target lectins, the design of multivalent inhibitors can be performed on a customized level, where the selection of the proper spacer is based on the information

S-Fluorenylmethyl protection of the cysteine side chain upon N^α-Fmoc deprotection

• Johannes W. Wehner and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2012, 8, 2149–2155, doi:10.3762/bjoc.8.242

• methods, NCL or SPPS. In addition, mannosidic glycoamino acids are of interest as ligands for mannose-specific lectins in solution [17] as well as for the fabrication of glycoarrays on solid support [10][18][19]. Moreover, we are interested to advance glycoamino acid deriatives such as 3 into ligands that

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• ; cyclodextrins; lectins; molecular recognition; multivalency; vesicles; Introduction The surface modification of materials with carbohydrates has attracted much attention due to the fact that such materials can be compared to and compatible with the cell surface [1]. The “glycocalyx” is a dense layer on the

• role of oligosaccharides on cell surfaces is the fact that human blood types (A, B, AB and 0) are solely determined by minor changes in the composition of the erythrocyte glycocalyx. Additionally, many biological mechanisms are mediated by multivalent recognition of carbohydrates. For example, lectins

• be readily obtained from jack-beans. It has four identical binding sides and binds α-mannose, α-glucose and their derivatives. Because of the importance of carbohydrates and their multivalent recognition by lectins in physiological processes, they are also considered a promising tool for the

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

• 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

• templates in vaccine development [67][68][69][70], and glycomimetics that block specific enzymes or lectins can be used for therapeutic purposes [71][72][73][74][75][76][77]. The Glycan Pathway Prediction (GPP) tool of the RINGS portal [78] can be used to predict glycans that can be obtained with a given

• , 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

• ; cluster effect; lectins; multivalency; Introduction The recognition of carbohydrate structures by carbohydrate binding proteins (lectins) plays a fundamental role in numerous intra- and intercellular events during development, inflammation, immune response, cancer metastasis, and pathogen–host

• (WGA), besides other plant lectins such as Con A, has been intensively employed as a model lectin to study the influence of the structure of multivalent ligands on the binding affinity. WGA ligands of defined structure containing two to twelve GlcNAc residues obtained either by individual synthesis [28

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

• among cells are mediated by binding of proteins such as lectins to oligosaccharides. Upon progression to higher malignancy, the glycosylation patterns of glycoproteins and glycosphingolipids on tumor cell surfaces undergo several alterations [6]. These changes are closely associated with distinct

• 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

• ]. Furthermore, the overexpression of the charged blood group antigen sialyl Lewisx consisting of the terminal NeuNAcα2-3Galβ1-4(Fucα1-3)GlcNAc-group is correlated with carcinogenesis. It is recognized and bound by selectins, which are a subgroup of lectins that play an important role as cell-surface molecules

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

• epitopes on glycoproteins and glycolipids are based on N-acetyllactosamine units (LacNAc; Galβ1,4GlcNAc) and often present on extended poly-LacNAc glycans ([Galβ1,4GlcNAc]n). Poly-LacNAc itself has been identified as a binding motif of galectins, an important class of lectins with functions in immune

• ][5]. Poly-LacNAc itself was identified as a recognition motif of galectins, which are an important class of mammalian lectins [6][7]. Another LacNAc related epitope is LacDiNAc (GalNAcβ1,4GlcNAc), which is especially well-known from parasitic nematodes and trematodes [8][9]. In humans, LacDiNAc

• reaction mixture leads to the formation of α,β-unsaturated aldehydes. By branching, the avidity of glycans has been shown to increase, which is important for the binding affinity of lectins [56][57]. The chemically branched poly-LacNAc glycans may, moreover, serve as analogues to naturally occurring I