Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• enzymatic degradation, and their ability to form intermolecular staples by backbone hydrogen bonding. This might be of special advantage to target or imitate multivalent and/or cooperative processes. As an initial effort, we equipped the cyclic β-tripeptide with a fluorophore and a protected cell

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

• be modified by host–guest interactions with functional guest molecules. In this article, we investigate the multivalent interaction of the lectin concanavalin A (ConA) with cyclodextrin vesicles decorated with mannose–adamantane conjugates with one, two or three adamantane units as well as one or two

• multivalent interaction with ConA, and the most efficient interaction (i.e., fastest agglutination at lowest concentration) was observed for mannose–adamantane conjugates, in which both the cyclodextrin–adamantane and the lectin–mannose interaction is inherently multivalent. Keywords: carbohydrates

• 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

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

• rigidification of the dendrimer structure and the iminosugar presentation in the clusters. The combination of the supramolecular properties of calixarenes with the advantage of a dendrimeric presentation of repetitive units opens up the possibility of generating well-defined multivalent and multifaceted systems

• 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

• interactions [10], the effect of iminosugar-based multivalent inhibitors on enzyme activity is difficult to rationalise. However, the introduction of several copies of an N-alkyl analogue of iminosugar 1-deoxynojirimycin onto a fullerene ball [8] or onto β-cyclodextrin [9] afforded the first pieces of evidence

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

• enhancements of the multivalent ligands with their ability to bind to the protein in a chelating mode. The best WGA ligand is a trivalent cluster with an IC50 value of 220 nM. Calculated per mol of contained chitobiose, this is the best WGA ligand known so far. Keywords: carbohydrates; click chemistry

• 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

• ligands for the Shiga-like [14][15] and cholera toxins [16][17] both belonging to the AB5 family of bacterial toxins. The frequent observation that the binding affinity of a multivalent ligand increases exponentially with the number of binding sites has been termed the glycoside cluster effect [18][19

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

• , tripalmitoyl-(S)-glyceryl lipopeptide Pam3-Cys-Ser-(Lys)4 (Pam3CSK4) and carrier proteins, such as tetanus toxoid (T.Tox.), have been successfully applied in MUC1 anti-tumor vaccines [28][29][30]. TH-cell peptides included in two- or three-component vaccines and multivalent glycopeptide dendrimer vaccines have

• resistant to tumor growth compared to control mice [37]. Vaccines with multivalent MUC1 T- and TN-glycopeptides were efficiently conjugated through azide/alkyne click chemistry to the Pam3CSK4 lipopeptide immune-stimulant. The recently reported vaccines are currently under immunological investigation [38

• , and, in addition, the peptide backbone of the glycoprotein is sometimes a part of the binding recognition domain. Synthetic glycopeptides with natural multivalent presentation of glycan structures may function as tools for the investigation of protein-binding events. Applications of glycopeptides in a

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

• : chemoselective ligation; click chemistry; cyclopeptide; heteroglycocluster; oxime; Introduction Multivalent interactions between carbohydrates and proteins play key roles in diverse biological events, including fertilization, cell–cell communication, host–pathogen interactions, immune response and cancer

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

• these concepts are not only molecular recognition and the noncovalent bonds themselves, but also self-assembly, self-sorting, templation and multivalent binding [1][2][3][4][5][6][7][8]. Consequently, the reductionist investigation of synthetic supramolecules can help us to understand biological systems

• better. Such a synthetic approach can also help in the investigation of multivalent binding [9][10][11][12], because the number of binding sites can be altered at will, and studies can be done with a suitable series of host and guest molecules in which the nature and number of binding sites is

• ], between the single building blocks is necessary for efficient templating effects, which aim at assembling higher-order molecular architectures. The synthesis of a multiply threaded architecture [80][81] thus requires multivalent wheel and axle components as precursors, which are also interesting with

Supramolecular chemistry II

• Christoph A. Schalley

Beilstein J. Org. Chem. 2011, 7, 1541–1542, doi:10.3762/bjoc.7.181

• sciences on the other. In the life sciences, the networks of noncovalent interactions between the constituents of cells, for example, have shifted into the current focus. Self-assembly, templation, self-sorting and multivalent binding all contribute to setting up the extremely complex architecture of a

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

• 1 fimbriae with a monovalent carbohydrate recognition domain (CRD) that is known from X-ray studies. However, binding studies with multivalent ligands have suggested an additional carbohydrate-binding site on this protein. In order to prove this hypothesis, a bivalent glycopeptide ligand with the

• -mannosyl moiety, for example, the terminal mannoside residues of high-mannose-type glycoproteins of the glycocalyx [12]. However, the precise nature of the ligand-receptor interactions is not fully understood. For example, when multivalent carbohydrate ligands were tested as ligands of FimH and type 1

• 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

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• (particle diameter 6 nm). After sulfation of the hydroxyl groups the multivalent conjugates obtained displayed strong binding to P- and L-selectins, thus demonstrating that compounds such as 24 and 28 are of interest for the development of new anti-inflammatory agents [27][28]. Inspired by these first

RAFT polymers for protein recognition

• Alan F. Tominey,
• Julia Liese,
• Sun Wei,
• Klaus Kowski,
• Thomas Schrader and
• Arno Kraft

Beilstein J. Org. Chem. 2010, 6, No. 66, doi:10.3762/bjoc.6.66

• the protein surface – in other words they encourage polymer/protein self-assembly in order to maximize attractive noncovalent interactions. A second major advantage of multivalent polymeric hosts is their rapid and efficient synthesis at low cost as well as the high proteolytic stabilities of most

• could be detected for the short version, indicating that size matters and promotes multivalent or cooperative binding. Finally, the protein series was extended to lysine-rich histone (pI 10), lysozyme (pI 9), proteinase K (pI 8) and bovine serum albumin or BSA (pI 6). Again, the strong binders B20CH15

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

• . These copolymers are water soluble. Recognition of PCL nanoparticles by concanavalin A Lectins are proteins of non-immunological origin, able to bind carbohydrate ligands, without any enzymatic or immunological function. They are multivalent and can bind several ligands simultaneously and participate in

Synthesis in the glycosciences

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2010, 6, No. 16, doi:10.3762/bjoc.6.16

• structural diversity found in the carbohydrate regime is unparalleled [1] which makes the biological study of carbohydrate recognition and understanding the processes involved rather complicated. In addition, the multivalent nature of most carbohydrate ligands constitutes a special challenge in glycoscience

Thematic series on supramolecular chemistry

• Christoph A. Schalley

Beilstein J. Org. Chem. 2009, 5, No. 76, doi:10.3762/bjoc.5.76

• successfully transferred to neutral and anionic hosts. Nowadays, multivalent interactions start to play a significant role for host-guest chemistry. But supramolecular chemistry is much more than molecular recognition. Concepts such as templated synthesis, (hierarchical) self-assembly, and self-sorting have