Multivalency as a chemical organization and action principle
Multivalency is a key principle in nature to establish strong, but also reversible chemical interactions between two units, e.g., a receptor and a ligand, viruses and host cells, or between two cell surfaces. Multivalent binding is based on multiple simultaneous molecular recognition processes and plays an important role in the self-organization of matter, in biological recognition processes as well as in signal transduction in biological systems. The targeted development of multivalent molecules is not only used for the strong inhibition of proteins and prevention of pathogen infections, but also allows for the selective production of functional molecular architectures and surface structures as well as the controlled interaction of multivalent surfaces. In the future a deeper understanding of multivalent interactions at all length scales from the nanometer to the micrometer range is crucial for solving important problems and for the development of new systems in the fields of life and materials science.
See also the Thematic Series:
Multivalent glycosystems for nanoscience
- Letter
- Published 29 Apr 2015
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Figure 1: Volume size distribution profile of C18-PeBGF at a concentration of 20 µM in PBS (10 mM, pH 7.4).
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Figure 2: Negative staining transmission electron micrographs (TEM) of fibrillar (left) and sheet-like struct...
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Figure 3: Amphiphilic inhibitors induce aggregation of viruses. R18 labeled influenza virus was incubated wit...
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Figure 4: Inhibition constants KiHAI of C18-PeBGF, C18-s2s, C18-rs2s and EB against Aichi H3N2 and Rostock H7...
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Figure 5: C18-PeBGF mediated protection from infection of MDCK cells by Rostock H7N1 and Aichi H3N2. MDCK II ...
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Figure 6: Fluorescence microscopy images of GUVs (left) and human erythrocytes (right) after incubation with ...
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Figure 7: Hemolytic activity of stearylated peptides and EB. 2% human erythrocytes were incubated for one hou...
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- Full Research Paper
- Published 30 Apr 2015
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Scheme 1: Synthesis of hexasaccharide 10. Conditions: a) TfOH, NIS, 4 Å molecular sieves, DCM, 0 °C to rt; b)...
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- Published 04 May 2015
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Figure 1: Terminal sialic acids are typically α-(2,3) or α-(2,6) linked to galactose (Gal) such as in the tum...
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Scheme 1: (a) FmocCl, py, CH2Cl2, rt, 4 h, 77%, (b) 2-chloroacetyl chloride, py, CH2Cl2, 0 °C to rt, 3 h, 88%...
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Scheme 2: Automated synthesis of oligosaccharides with α(2,3)-, α(2,6)-sialic acid linkages. Glycosylations: ...
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- Full Research Paper
- Published 05 May 2015
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Scheme 1: General approach to divalent or trivalent carbohydrate mimetics on the basis of aminopyran 1 or ser...
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Scheme 2: Hydroxy group protection of aminopyran 1 to give compound 3, synthesis of amide 4 and subsequent de...
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Scheme 3: Attempt to synthesize protected divalent compound 6. Conditions: a) succinic acid dichloride, Et3N,...
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Scheme 4: HATU-mediated synthesis of divalent amide 25 and trivalent amides 27 and 29. Conditions: a) HATU, Et...
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Scheme 5: Polysulfations of amides 5 and 13. Conditions: a) 1) SO3∙DMF, DMF-d7, 1 d, rt; 2) 1 M NaOH, 0 °C; 3...
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Scheme 6: Polysulfation of divalent amides 21 and 22 leading to tetrasulfated amides 32 and 33. Conditions: a...
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Scheme 7: Conversion of trivalent compound 27 into nonasulfated carbohydrate mimetic 34. Conditions: a) 1) SO3...
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Figure 1: Structures of O-sulfated divalent amide 32 and trivalent amide 34 and their respective IC50 values ...
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- Full Research Paper
- Published 06 May 2015
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Figure 1: N-Bu DNJ (1) and examples of potent multivalent pharmacological chaperones and CFTR correctors (2 a...
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Figure 2: Azide-armed DNJ derivatives 4 and polyalkyne “clickable” scaffolds 5 and 6.
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Scheme 1: Synthesis of trisubstituted BODIPY derivatives. (a) ICl, CHCl3/MeOH, rt, 15 min, quantitative; (b) ...
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Scheme 2: Synthesis of DNJ clusters 13: (a) CuSO4·5H2O cat., sodium ascorbate, THF/H2O (1:1), 83% (12a), 56% (...
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Scheme 3: Synthesis of DNJ clusters 15: (a) CuSO4·5H2O cat., sodium ascorbate, DMF/H2O (6:1), 80 °C (MW) or r...
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Figure 3: a) Absorption (orange line), corrected emission (green line) (λexc = 510 nm), excitation (dashed bl...
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Figure 4: a) Absorption (orange line), corrected emission (green line) (λexc = 360 nm) and excitation (dashed...
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- Full Research Paper
- Published 07 May 2015
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Figure 1: Cartoon of a divalent carbohydrate-scaffolded molecular architecture that allows control of the fle...
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Scheme 1: Synthesis of carbohydrate-scaffolded dimeric thymine 7 and intramolecular photocycloaddition. The i...
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Figure 2: 1H NMR spectra (all in D2O, 500 MHz) of mannoside 7 (A) and of the irradiation product (8) after 3 ...
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Scheme 2: Synthesis of carbohydrate-scaffolded dimeric glycothymine 13 and intramolecular photocycloaddition....
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Figure 3: 1H NMR spectra (all in D2O, 500 MHz) of mannoside 13 (A) and of the irradiation product (14) after ...
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- Published 07 May 2015
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Figure 1: A) Schematic drawing of a bifunctional anchor molecule and its immobilization on a nanoparticle (NP...
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Scheme 1: Synthesis of tripodal catecholates for surface immobilization. PEG-triscatecholate 3 was synthesize...
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Scheme 2: Synthesis of tripodal catecholate platforms 11 and 13 for surface functionalization.
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Figure 2: Catecholates for the immobilization on ZnO NPs.
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Figure 3: A) XRD pattern of ZnO NPs obtained by the colloidal suspension of Zn(acac)2. B) TEM image of pure Z...
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Figure 4: A) TGA data of catecholates 3, 13 and 14 immobilized on ZnO NPs: pure ZnO NPs treated with MOPS buf...
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Figure 5: A) TGA data of catecholates 3 and 14 immobilized on ZnO NPs: pure ZnO NPs treated with MOPS buffer ...
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Figure 6: TEM images of ZnO NPs. A) ZnO NPs coated with monomeric PEG-catecholate 14 after washing with water...
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- Full Research Paper
- Published 08 May 2015
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Figure 1: Structures of the mono- and divalent guest and host molecules. The linker in the divalent guest mol...
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Figure 2: Optimized gas phase structures (TPSS-D3(BJ)/def2-TZVP) of the divalent complexes n0@DiC8, n1@DiC8 a...
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Figure 3: Double mutant cycle for n0@DiC8. The K variables are declared in Table 4 and are used in Equation 1. Top left: n0@Di...
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Figure 4: Optimized gas-phase structures for unfolding the monovalent (first row) and divalent (second row) h...
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- Full Research Paper
- Published 08 May 2015
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Scheme 1: Schematic representation of self-sorting effects in metallosupramolecular self-assembly processes.
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Scheme 2: Schematic representation of our approach to discrete heteroleptic oligonuclear metallosupramolecula...
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Figure 1: Tröger’s base-derived bis(phenanthroline) ligand (rac)-1 and bis(bipyridine) ligand 2.
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Scheme 3: Synthesis of chiral bis(phenanthroline) ligand (rac)-1 from 3.
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Scheme 4: Synthesis of bis(bipyridine) ligand 2 from 2-aminopyridine (4).
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Figure 2: NMR spectra (500.1 MHz in DMSO-d6 at 295 K) of free ligands b) (rac)-1 and c) 2; 1:1 mixtures of li...
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Figure 3: ESI mass spectrum (positive ion mode) of a 1:1:2 mixture of (rac)-1, 2, and CuBF4 sprayed from a 10...
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Scheme 5: Summary of the coordination behavior of the two ligands 1 and 2 and their equimolar mixture towards...
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- Letter
- Published 11 May 2015
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Figure 1: Phage display was used to find an optimized binding partner for FBP21-tWW. A) Schematic representat...
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Scheme 1: Schematic representation of the synthesis of hPG-peptide conjugate 2.
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Figure 2: A) ITC measurement with FBP21-tWW and hPG-peptide conjugate 2, the KD value is 17.6 ± 0.016 μM. B) ...
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- Review
- Published 11 May 2015
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Figure 1: DNA display of glycans.
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Scheme 1: Synthesis of glycoconjugate DNA by diazo-coupling.
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Scheme 2: β-Galactose-modified deoxyuridine phosphoramidite used for solid-phase DNA synthesis and DNA displa...
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Scheme 3: (NHS)-carboxy-dT phosphoramidite as a general entry for the solid-phase synthesis of glycan–DNA con...
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Figure 2: Multivalent triangular glycoDNA assemblies.
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Scheme 4: Preparation of the DNA glycoconjugate by CuAAC.
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Scheme 5: DNA glycoconjugation by sequential CuAAC.
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Scheme 6: Selection with modified glycoconjugate aptamers (SELMA).
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Scheme 7: Synthesis of PNA glycoconjugates (Mtt: 4-methyltrityl; R = H or (oligo)saccharide).
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Figure 3: DNA display of PNA-tagged glycans designed to emulate HIV's gp120 epitope.
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Figure 4: Combinatorial assembly and selection of two PNA glycoconjugate libraries on DNA templates.
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Figure 5: DNA display of ligand bridging opposing binding sites in a lectin (ECL).
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Figure 6: A glycan array prepared by hybridization of glycan–DNA conjugates and screening of RCA120.
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Figure 7: Multivalent sugar-core glycoconjugate DNA.
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Figure 8: Combinatorial self-assembly of PNA glycoconjugates on a DNA microarray.
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Figure 9: General scheme of the 10,000 member PNA-encoded glycoconjugate library.
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Figure 10: Oligomeric interaction with arrayed mono- and divalent ligands (represented as the black spheres) a...
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- Full Research Paper
- Published 12 May 2015
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Figure 1: SCP adhesion measurement sketch (top): A mannose-functionalized PEG-SCP sediments onto a Concanaval...
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Scheme 1: PEG functionalization is based on radical benzophenone photochemistry and subsequent addition of ca...
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Figure 2: A) ATR–FTIR spectroscopy signifying carbonyl group at around 1720 cm−1 and successful grafting; B) ...
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Figure 3: A) CA functionalization degree as a function of the irradiation time. The solid line represents an ...
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Figure 4: A) Increased mannose densities as schematically shown lead to increased contact areas. For the PEG-...
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- Published 12 May 2015
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Scheme 1: Synthesis of hyperbranched polyglycerol-supported and G1 dendronized imidazolidin-4-ones 4a–c and 8...
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Scheme 2: Synthesis of tyrosine-based imidazolidin-4-one 5. Reaction conditions: (a) 9 (1.0 equiv), MeNH2 (5....
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- Published 12 May 2015
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Figure 1: The structure of galectin-1. Reproduced with permission from [21]. Copyright 2004 Elsevier.
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Figure 2: (a) Generation 2 PAMAM dendrimer. (b) Lactose-functionalized dendrimers 1–4. Color-coding correspon...
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Figure 3: Average diameter (nm) of multivalent galectin-1 nanoparticles formed with multivalent glycodendrime...
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Figure 4: Representative fluorescent micrographs of glycodendrimer mediated galectin-1 nanoparticles. Nanopar...
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Figure 5: Comparison of average nanoparticle diameter (nm) formed with 4 measured by FM (blue) and DLS (diago...
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Figure 6: Lactose inhibition of galectin-1 nanoparticle formation with compound 4.
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Figure 7: Cellular aggregation assays with DU145 human prostate carcinoma cells. Cancer cell aggregation assa...
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Figure 8: Schematic representation of galectin-1/glycodendrimer aggregates at varying stoichiometries.
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Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks
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- Published 12 May 2015
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Figure 1: Mono-, di-, and tetravalent axles A1, A2 and A4 and mono-, di-, and tetravalent hosts C1, C2 and C4...
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Scheme 1: Overview of the synthesis of the guests A2 and A4. a) Pyrrole (4), BF3·Et2O, DDQ, CHCl3, rt; b) Zn(...
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Scheme 2: Synthesis of crown ether hosts C4 and C2: a) K2CO3, LiBr, 17, 2-[2-(2-chloroethoxy)ethoxy]ethanol, ...
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Figure 2: Schematic representation of the host–guests complexes. Top: complexes A2@C12, A4@C14, A12@C2 and A14...
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Figure 3: 1H NMR (500 MHz, 298 K, CD2Cl2, 3 mM) of a) C1 (top), A2@C12 (middle) and A2 (bottom); b) C1 (top), ...
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Figure 4: 1H NMR (500 MHz, 298 K, CD2Cl2, 3 mM) of a) C2 (top), A12@C2 (middle) and A1 (bottom) and b) C4 (to...
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Figure 5: Normalized UV–vis absorption spectra (CH2Cl2, 3 μM) of A2, A4, C2 and C4 and their complexes formed...
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Figure 6: ESI-Q-TOF-MS spectra (CH2Cl2, 0.2 µM; left hand side) and respective experimental and calculated is...
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Figure 7: 1H NMR (500 MHz, 298 K, CD2Cl2, 1 mM) of a) C4 (top), A22@C4 (middle) and A2 (bottom); b) C2 (top), ...
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Figure 8: 1H NMR (500 MHz, 298 K, CD2Cl2, 1 mM) of a) C4 (top), A4@C4 (middle) and A4 (bottom) and b) C2 (top...
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Figure 9: Normalized UV–vis absorption spectra (CH2Cl2, 2 μM) of the guests A2 and A4 (black), the hosts C2 a...
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Figure 10: ESI-Q-TOF-MS spectra (CH2Cl2, 0.2 µM; left hand side) and respective experimental and calculated is...
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Video
- Full Research Paper
- Published 13 May 2015
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Scheme 1: Synthesis of multivalent arginine and histidine functionalized dPG-NH2 50%. The depicted dPG-NH2 re...
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Figure 1: Agarose gel electrophoresis retardation assay of AAdPGs/siRNA polyplexes. (A) dPG-13Arg13His, (B) d...
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Figure 2: Size measurements of dPG-NH2 50% and AAdPGs/siRNA complexes. Intensity distributions of all polyple...
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Figure 3: The result of MTT assay on a NIH 3T3 cell line transfected with AAdPG, dPG-NH2 50%, and 90%/siRNA p...
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Figure 4: Cell viability versus transfection efficiency of dPG-8Arg30His and dPG-NH2 90% at N/P ratio 30.
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Figure 5: Summary of transfection results versus viability of AAdPGs with various Arg and His composition rat...
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Figure 6: Confocal images of NIH 3T3 cells treated with Cy3-siRNA/vector complexes: (A) naked siRNA, (B) lipo...
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- Review
- Published 13 May 2015
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Figure 1: Differentiation potential of mesenchymal stem cells (MSCs) in bone marrow. MSCs can differentiate i...
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Figure 2: (a) The structure of the integrin heterodimeric receptors with α and β subunits. (b) The major inte...
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Figure 3: The chemical structure of the α5β1-selective (left) and the αvβ3-selective (right) peptidomimetics....
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Figure 4: When the distance between two neighboring integrin ligands is <70 nm, the focal adhesions and contr...
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Figure 5: (a) BMP-2 homodimer. 3D-Structure of a BMP-2 homodimer (blue and pink) with cysteine residues, high...
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Figure 6: Growth factors, e.g., BMP-2, can be immobilized on the substrates to mimic the matrix-bound form (l...
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- Published 13 May 2015
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Scheme 1: Protein design and dual-functionalization of TTL: periodate cleavage, oxime ligation and CuAAC.
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Figure 1: Dual-functionalization of TTL: A) MALDI–MS spectra (red: modified protein (as marked below); black:...
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Figure 2: SPR measurements: A) set-up showing different binding events of the double-functionalized TTL to EC...
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- Published 15 May 2015
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Figure 1: Helical wheel representation and sequences of the peptides used in this study.
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Figure 2: CD spectra of 30 µM peptide VW05, R1A3, R2A2, R2A3, R2A4 and R2A5 at (A) pH 9 and (B) pH 11 in 10 m...
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Figure 3: (A) TEM of 100 µM R2A2 in 10 mM Tris/HCl buffer, pH 9. Sample was negative stained with 2% PTA; def...
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Figure 4: (A) Dynamic light scattering of 0.05 µM Au/MUA nanoparticles at pH 9. (B) Cryo TEM image of 0.05 µM...
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Figure 5: CD spectra of 15 µM peptide in the presence 0.05 µM Au/MUA nanoparticles at pH 9 after (A) 0 hours ...
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Figure 6: Agarose gel of (A) VW05, (B) R1A3, and (C) R2A2 in the presence of 0.05 µM Au/MUA nanoparticles at ...
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Figure 7: Cryo TEM images of 100 µM R2A2 and 0.05 µM Au/MUA nanoparticles at pH 9 at a defocus of (A) −1.2 µm...
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- Published 15 May 2015
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Figure 1: (a) Schematic of a divalent ligand–receptor system: The receptor has two binding pockets with a dis...
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Figure 2: Effective concentration Ceff of spacers with a contour length of L = 5 nm as a function of the dist...
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Figure 3: Average end-to-end distance, rete, end-to-end-distance where the effective concentration Ceff exhib...
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Figure 4: Effective concentration for the optimized average end-to-end distance rete=d for the wormlike chain...
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Figure 5: Relative binding affinity (RBA) of a divalent ligand in dependence of the end-to-end distance of th...
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Figure 6: Efficiency diagram:
![[Graphic 33]](/bjoc/content/inline/1860-5397-11-90-i83.png?max-width=637&scale=1.18182)
is shown for different ligand–spacer constructs. If the monovalent dissociatio...
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- Published 15 May 2015
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Figure 1: Expected coordination complexes of monovalent and bivalent structures (1 and 2a–c, respectively) wi...
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Scheme 1: Synthesis of pyridine-PEG conjugate 5.
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Scheme 2: Synthesis of pyridine-PEG conjugate 10.
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Figure 2: Principle of the SMFS experiment. During retraction of the sample, possible interactions are probed...
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Figure 3: Potential energy diagrams according to the KBE model for simultaneous and successive bond rupture a...
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Figure 4: Most probable rupture forces plotted over their corresponding loading rate. Each point denotes for ...
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Figure 5: Possible rupture mechanism describing the extraordinary long rupture length of system 2c. Starting ...
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Figure 6: Most probable rupture forces at a logarithmic loading rate of 8.5 in relation to the corresponding ...
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- Full Research Paper
- Published 18 May 2015
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Figure 1: A) A maximum rupture force (max force) histogram for a dopamine-functionalized tip is given for the...
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Figure 2: A) Maximum force histograms for the different dwell times indicated in the inset normalized to the ...
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Figure 3: Schematics of the different possibilities for attachment via multiple catechols. A) Multivalent att...
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Figure 4: A) Force–distance curves where the rupture is not smooth but rather interrupted by a cluster of mea...
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- Published 18 May 2015
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Figure 1: Comparing the entropy loss during ligand–receptor interactions in dependence of the rigidity of the...
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Scheme 1: Selection of three polymer carriers differing with respect to backbone flexibility, and morphology ...
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Figure 2: Representative ITC-measurements conducted at 8 °C with the peptide–polymer conjugates A) pHPMA-1 an...
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Figure 3: Enthalpic and entropic contributions to the free energy of binding processes of multivalent peptide...
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Figure 4: MD simulations over time (0–100 ns) yielding A) the mean sulfur distance between two peptides at th...
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Figure 5: MD simulation image showing the interaction of two dextran–peptide conjugates with three tandem WW ...
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