Self-assembly of heteroleptic dinuclear metallosupramolecular kites from multivalent ligands via social self-sorting

• Christian Benkhäuser and
• Arne Lützen

Beilstein J. Org. Chem. 2015, 11, 693–700, doi:10.3762/bjoc.11.79

• social self-sorting manner as evidenced by NMR spectroscopy and mass spectrometry. Keywords: metal complexes; multivalency; self-assembly; self-sorting; supramolecular chemistry; Tröger's base; Introduction Self-assembly of defined aggregates from multicomponent mixtures through self-sorting effects

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• . Keywords: bifunctional anchors; catecholates; multivalency; poly(ethylene glycol); ZnO nanoparticles; Introduction An elegant approach to generate tailored materials and nanoparticles is the formation of molecular monolayers by chemisorption of bifunctional anchor molecules (Figure 1A) [1]. The

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

• Anna K. Ciuk Thisbe K. Lindhorst Christiana Albertina University of Kiel, Otto Diels Institute of Organic Chemistry, Otto-Hahn-Platz 3/4, D-24118 Kiel, Germany, Fax: +49 431 8807410 10.3762/bjoc.11.75 Abstract Multivalency effects are essential in carbohydrate recognition processes as occurring

• dimerized by [2 + 2] photocycloaddition. Thus, thymine functions as a control element that allows to restrict the conformational flexibility of the scaffolded sugar ligands and thus to “organize” multivalency. With this work we add a parameter to multivalency studies additional to valency. Keywords: [2 + 2

• ] photocycloaddition; carbohydrate scaffolds; multivalency; thymine glycoconjugates; Introduction Multivalency of molecular interactions is a fundamental principle in carbohydrate recognition. It influences the avidity and specificity of carbohydrate–protein interactions as well as it enables supramolecular changes

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• ; fluorescent probes; iminosugars; 4-methylumbelliferone; multivalency; pyrene; Introduction Since the isolation in the 1970’s of 1-deoxynojirimycin (DNJ) from natural sources and the finding of its biological activity as an α-glucosidase inhibitor, thousands of sugar mimetics with a nitrogen atom replacing

• per DNJ unit) [11][12]. In the following years, an impressive ever-growing number of multivalent iminosugars based on various scaffolds, ligands and linkers have been synthesized to further investigate the impact of multivalency on glycosidase inhibition [9][10][11][12][13][14][15][16][17][18][19][20

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

• ; multivalency; selectins; sulfation; Introduction In a series of publications [1][2][3][4][5][6] our group reported on the syntheses of carbohydrate mimetics [7][8][9][10][11] that are based on aminopyrans, aminooxepanes or other aminopolyols. These compounds and their conjugates were prepared to be examined

• smaller inhibitors than the above mentioned nanoparticles and also to examine multivalency effects [25][26]. Several of these compounds could successfully be sulfated and tested as L-selectin inhibitors. Results and Discussion Aminopyran 1 was easily available following the previously reported synthetic

• multivalency effect is not evident and a sound structure–activity discussion is not feasible as the two compounds have different end groups and different flexibilities. A series of related compounds is required to have a better understanding of structure–property relationships and the influence of multivalency

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• : azide; click chemistry; extracellular matrix; hexasaccharide; hyaluronan; multivalency; Introduction Much effort has been exerted during the last years to refine current knowledge about the biology of the extracellular matrix (ECM) [1]. While in the past, it was only regarded as a “space filler” among

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• limitations of this type of self-assembling IAV inhibitors. Keywords: amphiphilic peptide; antiviral; influenza virus; multivalency; self-assembled structures; Introduction Annually influenza A virus infections cause up to 500.000 deaths worldwide, and are therefore a serious threat, and burden to humans [1

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• , with non-complementary strands aggregates of higher stoichiometry are generated. Keywords: cooperativity; cyclodextrins; molecular recognition; multivalency; sequence specificity; Introduction Multivalency is the interaction of a receptor and a ligand with at least two recognition motifs on each

• binding partner [1]. In recent years multivalency has been recognized to play a major role in almost all biological processes, e.g., the recognition of cells by other cells, bacteria or viruses, the adhesion of cells or signal transduction pathways [2]. By the combination of multiple, rather weak non

• , such vesicles can be modified with bio-active ligands and serve as model systems to mimic biological processes on cell membranes [10][11]. In the field of materials science multivalency has been used to create functional polymers [12][13][14] and self-assembled electronic [15][16][17][18][19][20] or

Organophosphorus chemistry

• Paul R. Hanson

Beilstein J. Org. Chem. 2014, 10, 2087–2088, doi:10.3762/bjoc.10.217

• number of important fields. Among the more prominent features that elevate their status as a unique and versatile class of compounds, include variable oxidation states, multivalency, asymmetry and metal-binding properties. Their presence in bioactive natural products, endogenous biomolecules, small

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

• good affinity for Pseudomonas aeruginosa lectin lecA. They are convenient biological probes for investigating the roles of lecA and lecB in biofilm formation. Keywords: antibiotic; biofilm; glycocluster; lectin; multivalency effect; multivalent glycosystems; Introduction Pseudomonas aeruginosa (PA

• is often based on the recognition of multiple epitopes through a synergistic and cooperative effect, called the ‘’glycocluster effect” [14][15][16]. It has been shown in a number of systems that multivalency effects can be exploited to obtain high-avidity synthetic ligands against various types of

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

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

• . Furthermore, we confirmed that in case of this specific lectin binding the presentation of lactose units on a cone calixarene is highly preferred with respect to its isomeric form in the 1,3-alternate structure. Keywords: glycocalixarenes; cluster glycoside effect; multivalency; click chemistry; surface

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

• azobenzene unit allows for the photosensitive control of glycoligand binding to protein receptors. These stimuli-sensitive glycoligands promote the understanding of multivalent binding and will be further developed as novel biosensors. Keywords: azobenzene; glycopolymer; lectin binding; multivalency

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

• ; galectin-3; glycodendrimers; multivalency; multivalent glycosylation; protein aggregation; Introduction The role of multivalency in biology is well established, and examples of this phenomenon abound [1]. The ability of multivalency to enhance weak interactions has been shown in a variety of

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• binary combinations of α-D-Man or β-D-GlcNAc, thus providing rapid access to attractive heteroglycosylated platforms for diverse biological applications. Keywords: chemoselective ligation; heteroglycocluster; multivalency; multivalent glycosystems; one-pot synthesis; Introduction Multivalent

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

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• . Keywords: cyclopeptoids; glycosidases; iminosugars; inhibitors; multivalency; mutivalent glycosystems; Introduction Within a few years, the field of multivalent glycosidase inhibitors has witnessed tremendous advancement. Since the report in 2009 of the first quantifiable multivalent effect in glycosidase

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

• , India Institute for Inorganic Chemistry, Georg-August University Göttingen, Tammannstraße 4, D-37077 Göttingen, Germany 10.3762/bjoc.10.93 Abstract Carbohydrate recognition is essential in cellular interactions and biological processes. It is characterized by structural diversity, multivalency and

• , xylose) as sugar-β-amino acids in a 314-helix. Up to three sugar units were linearly aligned with 5 Å distance (Figure 1). This kind of sugar organization will be of later relevance, e.g., in lectin binding studies and with respect to the investigation of multivalency effects [21][22][23]. The use of

• -helix. The sugar hydroxy groups permit additional interactions of the water-soluble peptides. Further, uniform orientation and defined distances of side-chain sugar residues offer the opportunity to use sugar functionalized peptide scaffolds to study multivalency in carbohydrate recognition. The glucose

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides. Keywords: continuous flow; flow chemistry: flow synthesis; glycoligands; multivalency; photochemistry; solid-phase synthesis; thiol–ene; thioglycosides; Introduction Multivalent carbohydrate ligand

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• ]. In this study we used carbohydrate templates for the design of multivalent antimicrobial peptides targeted to control plant and human pathogenic bacteria and explored whether multivalency enhances the antimicrobial activity. These multivalent constructs were obtained by preassembling the

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

• synthesized to study the effect of multivalency, each with a distinct number of adamantane or mannose functions. The adamantane unit can bind into the cavity of cyclodextrins embedded at the vesicle surface. Additionally, all guest molecules possess α-mannose units, which bind to lectins such as concanavalin

• between the mannose functions, similar to the average spacing obtained for guest 1. However, due to the inherent multivalency of guest 4, it should have a much higher affinity both for the cyclodextrin vesicle surface as well as for ConA. Indeed it was found that guest 4 ([4] = 10 μM) can induce 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

• with more complex and/or biologically relevant iminosugars. Keywords: calixarenes; cation-responsive system; dendrimers; iminosugars; multivalency; Introduction Polyhydroxylated pyrrolidines are one of the main classes of naturally occurring sugar mimics [1][2] and belong to the so-called iminosugars

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

• multivalent ligands with disproportionally enhanced avidity. A prerequisite for an effective multivalency effect, however, is that the linking spacer between the individual epitopes has the correct geometry to allow a simultaneous multipoint association, i.e., a chelating binding mode. Wheat germ agglutinin

• mentioning that we never observed precipitate formation during incubation of WGA with our synthetic ligands. This suggests that in our case intermolecular multivalency (cross-linking) plays a negligible role and that the main mechanism of affinity enhancement is chelating binding to the same WGA dimer. The

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

• of diverse carbohydrate structures immobilized in a microarray format have made carbohydrates accessible for numerous functional studies of protein-binding recognition [90][91][92]. In addition to the glycan structure, multivalency and orientation are important for the presentation of glycan ligands

• microarray format are desirable for such binding studies. Evaluation of antibody binding epitopes in vaccine and biomarker discovery is one recent example of glycopeptide microarrays [93][94]. Multivalency and orientation for glycan presentation have been shown to be important for the inhibition of microbe

• patient samples. Binding studies to GM1 ligands have clearly demonstrated the importance of multivalency in protein–carbohydrate binding recognition [95][96][97][98][99][120]. In one study, a 380,000 (47,000/sugar)-fold affinity enhancement and an IC50 of 50 pM was reported, by comparison of a GM1

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• wheel precursors. Keywords: multivalency; pseudorotaxanes; Sonogashira coupling; supramolecular chemistry; tetralactam macrocycles; Introduction Synthetic supramolecular complexes have the great potential to put those concepts to the test that govern much of the noncovalent chemistry in nature. Among

• respect to their binding properties. Among the examples of such multivalent pseudorotaxanes [80][81][82], the “molecular elevators” reported by Stoddart et al. [83][84] are particularly fascinating, because they combine multivalency with the ability of a molecular device to respond to external stimuli, in

• this approach. With our toolbox, the number and position of binding sites can be varied systematically; hence, the toolbox provides a means to examine multivalency. However, despite the fact that there is qualitative evidence for pseudorotaxane formation, the binding motif is not yet optimal for a