Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• -selectin binders; multivalency; self-assembly in water; supramolecular polymers; Introduction Deciphering the interaction of artificial molecular building blocks with biological components is a key element on the way to understanding and selectively manipulating biological systems. Throughout nature

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• buffer and also in buffer containing 150 mM NaCl at physiological pH value. Furthermore, the multivalent aggregates demonstrated a significant selectivity in ATP detection over ADP, AMP and pyrophosphate. Keywords: amphiphile; ATP; excimer; multivalency; self-assembly; Introduction Supramolecular anion

• general challenging to design high-affinity synthetic probes for anion sensing under such competitive conditions [7]. One of the strategies that has proven to be quite successful in this regard, not only for bio-anions, rather for a variety of several other analytes also, is multivalency [8][9][10][11

• systems and they have been frequently exploited for the highly sensitive detection of a diverse range of target analytes [16][17][18]. However, the covalent route often requires time consuming synthetic steps and hence, in recent years, self-assembled multivalency has emerged as a suitable alternative [19

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• ]. Switchable mechanically interlocked molecules (MIM) that rely on multivalency have been studied rarely, thus Chen et al. have reported the design and highly efficacious synthesis of a novel two-component, triply interlocked [2](3)catenane C–H3·6PF6 19 (Figure 16) by use of a pyrazine-extended triptycene

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• neoangiogenic vessels and in several human tumor cells [39][40]. It is well known that RGD-containing oligopeptides (RGD = Arg-Gly-Asp tripeptide pattern) bind selectively to αvβ3 integrin with a high affinity and a very high selectivity [41][42][43]. As multivalency enhances the binding strength of a ligand to

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• are reports of natural and designed molecules that display multivalency in DNA recognition by binding at more than recognition sites (minor groove, major groove or base pair insertion) [11][12][13]. In synthetic multivalent ligands, which are made to enhance DNA affinity, tether length and composition

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• particular emphasis on exploiting the multivalency of the toxin to enhance activity. In this review we introduce the structural features of the toxin that have guided the design of diverse inhibitors and summarise recent developments in the field. Keywords: carbohydrate; cholera; multivalency; toxin

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• , leading to a substantial improvement in the off-rate. Together with both a catch-bond mechanism (i.e., improvement of affinity under shear stress) and multivalency, two methods commonly utilized by pathogens, the affinity of the carbohydrate–FimH interaction can be further improved. Including those just

• ; multivalency; pre-organization; Review Recognition of carbohydrate ligands For the recognition of carbohydrate ligands, nature has explored binding sites of different shapes and properties. The large family of C-type lectins (CLECs) exhibits carbohydrate-recognition domains (CRDs) which incorporate a calcium

• in cell-to-cell recognition processes [11]. Although highly specific, its interaction with E-selectin exhibits a dissociation constant (KD) of only 800 μM [12]. To address this obstacle of low affinity, nature applies the principal of multivalency by providing several binding sites to the

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• demonstrated the ability of this AuNP based vaccine system to protect neonates born to vaccinated mothers from the bacteria [104]. In another study, the impact of multivalency on the ability of GAuNPs to induce immune cell responses in vitro was studied using highly pure NPs coated with non-immunoactive mono

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• mechanism underlying friction in the 12–CD configuration. Stick spike forces of 2 nN are enhanced by at least a factor of 3 compared to the one for the CD–CD system previously described [48]. This spike force may be enhanced by the multivalency effects discussed above, but its strength indicates that more

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• glycosidases. Keywords: dendrimers; glycosidase inhibitors; iminosugars; multivalency; piperidine alkaloids; Introduction Iminosugars are well-known naturally occurring glycomimetics with a nitrogen atom replacing the endocyclic oxygen, mainly recognized as inhibitors of carbohydrate-processing enzymes

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• -binding abilities, an improved affinity can be achieved by polytopic hosts [61][62][63] through multivalency effects in macrocycles. Olefin metathesis has played a key role in the development of cyclophane chemistry. Some of the catalysts used for this purpose are listed in Figure 3. The development of

Multivalency as a chemical organization and action principle

• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 848–849, doi:10.3762/bjoc.11.94

• Rainer Haag Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany 10.3762/bjoc.11.94 Keywords: glycoarchitectures; supramolecular chemistry; multivalency; multivalent protein inhibitors; pathogen binding; Multivalency is a key principle in nature

• (Figure 1). Also, the kinetically controlled dissociation can become very slow to almost non-existent. Multivalency is also dependent on the size, shape and flexibility of the scaffold architecture, especially for the interfacial interaction with biological systems. In order to obtain a deeper

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• superior to induce multivalent binding and to increase affinity, while the more flexible and dendritic polymers, pHPMA and hPG are suitable to induce crosslinking upon binding. Keywords: inhibitors of protein–protein interactions; isothermal titration calorimetry; multivalency; peptide–polymer conjugates

• ; proline-rich peptide sequences; Introduction Multivalency is a general principle in nature for increasing the affinity and specificity of ligand–receptor interactions [1]. Multivalent binding is characterized by the cooperative, over-additive enhancement of binding affinities of ligands and receptors in

• a defined spatial arrangement. The strongest affinity enhancement can be expected in the case of a perfectly fitting, rigid arrangement of ligands and receptors (Figure 1A). In such cases the affinity of the multivalent ligand can be potentiated by the degree of multivalency. Prominent examples for

Adsorption mechanism and valency of catechol-functionalized hyperbranched polyglycerols

• Stefanie Krysiak,
• Qiang Wei,
• Klaus Rischka,
• Andreas Hartwig,
• Rainer Haag and
• Thorsten Hugel

Beilstein J. Org. Chem. 2015, 11, 828–836, doi:10.3762/bjoc.11.92

• . In addition, we quantified the poly/multivalency of bonds and showed first steps towards controlling this valency. Notably, a very high percentage (40%) of catechol groups on hPGs must be introduced to obtain di- or trivalent interactions. The data also show that the dwell time of catechols in

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• systems. Keywords: molecular rupture mechanism; multivalency; malleability; pyridine coordination compounds; scanning force microscopy; Introduction In a multivalent molecular system, two partners interact with each other through two or more non-covalent equivalent interaction centers. This principle is

• important in biochemistry [1] and supramolecular chemistry [2], but still not fully understood on the level of individual non-covalent interactions [3]. Synthetic supramolecular systems are ideal for a quantitative analysis of multivalency on the level of single molecules, because specific ligand design can

• interactions is crucial for the specific design of ligands. Future studies will address specific backbone properties and higher valencies on the way to a deeper understanding of their influence on multivalency. Experimental Reactions were generally performed under argon in dried flasks. Solvents and reagents

Influence of length and flexibility of spacers on the binding affinity of divalent ligands

• Susanne Liese and
• Roland R. Netz

Beilstein J. Org. Chem. 2015, 11, 804–816, doi:10.3762/bjoc.11.90

• range as the size of a receptor binding pocket. Keywords: binding affinity; divalent ligand; effective concentration; multivalency; Introduction Multivalency is a common design principle in biological systems. The simultaneous binding of several, relatively weakly binding partners is a widely used

• strategy to strengthen the overall binding affinity [1][2][3]. Multivalency is believed to play an important role in evolutionary processes, since the collective interaction of several rather simple ligands makes the development of more complex binding partners with a higher binding affinity unnecessary [2

• ]. Also in drug design, the synthesis of artificial multivalent ligands is a promising route to increase the binding affinity or to reduce the amount of substance required for treatment [4][5][6][7]. The term multivalency is used for systems that consist of several identical binding partners. Thereby, the

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

• Daniel Schöne,
• Boris Schade,
• Christoph Böttcher and
• Beate Koksch

Beilstein J. Org. Chem. 2015, 11, 792–803, doi:10.3762/bjoc.11.89

• macrostructures. Keywords: coiled-coil peptides; α-helical fibrils; controlled aggregation; gold nanoparticles; multivalency; Introduction In the past few decades metal and semiconductor nanoparticles, including gold nanoparticles, have gained much interest due to their desirable optical, magnetic, and

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• modification; lectin; multivalency; Introduction The chemical modification of proteins has been developed to a core discipline in chemical biology with diverse applications in all areas of the life sciences, including pharmacology, biophysics, biotechnology and cell biology [1][2][3][4]. In addition to the

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• stoichiometry, while the amount of alternative structures can be neglected. Our results illustrate the power of multivalency to program the multicomponent self-assembly of specific entities into discrete functional nanostructures. Keywords: crown ethers; multicomponent assembly; multivalency; porphyrins

• significant attention mediated in particular by the desire to understand biological phenomena, such as virus docking to cells [27], toxin inhibition [28], or leucocyte recruitment in inflammation processes of the endothelium [29]. Multivalency has also inspired synthetic supramolecular architecture as it not

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

• galectin-1/glycodendrimer aggregates effectively alter the presentation of galectin-1 to cells, thereby altering the cells’ recognition events. Inhibition by monomeric lactose well illustrates the multivalency avidity enhancement. Monomeric lactose inhibited cell adhesion at a concentration of 6 mM, while

• glycodendrimers 1–4 have a strong influence on the native cellular adhesion mechanism. Conclusion The concept that multivalency can be used to effectively control cellular activities was investigated using lactose functionalized dendrimers. First, the ability of the multivalent framework to organize galectin-1

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• ; multivalency; Introduction In nature, multivalent architectures, e.g., enzymes, bacteria or viruses, are responsible for cooperative interactions between different interfaces or molecules [1]. The realization of the concept of multivalency has attracted attention from different fields ranging from medicine

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• to identify the key principles of carbohydrate/protein receptor interaction and to utilize carbohydrate structures as drugs, e.g., in cancer treatment or pathogen-related diseases [2][3]. A well-established key principle of carbohydrate–receptor interactions is multivalency. Natural carbohydrate

• ligands are typically oligomers consisting of multiple subunits of varying complexity. When binding to receptors this leads to a receptor clustering or so-called glycocluster effect. However, multivalency even goes further: For example when cells form contact layers of surface anchored carbohydrates the

• interfaces, the surface presentation and density of the binding partners. In this work, we focus on the latter aspects. More specifically, we study the effect of linker type and ligand density on the interaction between sugar-ligands and receptors on a surface. It is well known that multivalency and linker

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

• programmability of the assemblies lends itself to a combinatorial display of multiple ligands. Recent efforts in the synthesis and applications of such conjugates are discussed. Keywords: glycan; glycoconjugate; DNA display; multivalency; nucleic acid conjugates; oligomeric interaction; Introduction Cell

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• ± 6 μM in solution whereas it was 17 ± 0.016 μM for hPG-peptide conjugate 2, demonstrating an approximately tenfold overall affinity enhancement. However, when considering that ≈7 peptides are bound per nanoparticle, the actual multivalency effect is small. For both the monovalent ligand and the hPG

• and methods and supplementary figures. Acknowledgements Financial support from the German Research Foundation (DFG) through the SFB 765 “Multivalency” and the BMBF is gratefully acknowledged.

First principle investigation of the linker length effects on the thermodynamics of divalent pseudorotaxanes

• Andreas J. Achazi,
• Doreen Mollenhauer and
• Beate Paulus

Beilstein J. Org. Chem. 2015, 11, 687–692, doi:10.3762/bjoc.11.78

• multivalency [1] and is mainly observed in biochemical systems [2][3][4][5][6][7][8][9]. But the concept of multivalency can be transferred to supramolecular assemblies with suitable building blocks [10][11][12] including (pseudo)rotaxanes [13][14][15] as well. One common building block for pseudorotaxanes is

• , 298.15 K) and equilibrium constant K for the systems from the double mutant cycle.a Acknowledgements Support by the German Research Foundation (DFG) through the Collaborative Research Center (CRC) 765 'Multivalency as chemical organization and action principle: new architectures, functions and