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

• with peptide concentration. Isothermal titration calorimetry (ITC) was used to determine the thermodynamic parameters as well as the binding constant for the assembly of Au/MUA nanoparticles (Table 1). By fitting with a one set of binding site mode the binding stoichiometry N, the binding constant KB

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

• these aggregates. This indicates that nanoparticles formed using the mannose-functionalized dendrimer do not rely on interactions in the β-galactoside binding site on galectin-1 and that non-specific glycodendrimer/galectin-1 interactions are responsible for the formation of these small aggregates

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

• binding sites for glucosides and mannosides (preferred) spaced by 72 Å. Titration studies showed a clear dependence on the functionalization of each arm in the 3-way junction consistent with a synergistic interaction of each arm with a binding site. However, the number of glycan units (on each arm 3, 6 or

• 12) had marginal impact on the binding suggesting a saturation of binding site occupancy. For the structure with 6 units of maltose on each arm, a KD of 1 μM was measured which is 700-fold more potent (40-fold per sugar) than monovalent maltose. The advent of the copper-catalyzed azide–alkyne

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

• virus to the host cell proved to be potent drug candidates [4][5][6][7][8][9]. Those inhibitors bind to the virus envelope spike protein hemagglutinin (HA) which is organized as a homotrimer. In particular, inhibitors competing for the highly conserved binding site for sialic acid, which is the natural

Photocatalytic nucleophilic addition of alcohols to styrenes in Markovnikov and anti-Markovnikov orientation

• Martin Weiser,
• Sergej Hermann,
• Alexander Penner and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2015, 11, 568–575, doi:10.3762/bjoc.11.62

• distance dependant process, the photocatalyst might not be regenerated and hence removed from the catalytic cycle. This scenario could potentially be improved by a substrate binding site on the photocatalyst that keeps the substrate in the vicinity of Py as long as it is required for forward and back

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• as aryl moieties, with 2-naphthyl identified as the best pharmacophore for the series discussed above (Figure 1, D–I). Nevertheless, hydrogen bonds might also be created in this secondary binding site with other residues. The introduction of hydrogen bond donors and/or acceptors at the 5-position of

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• binding site or to the galactose acceptor site. Inhibitors of TcTS binding to the βGalp acceptor site would be highly selective, as other sialidases lack this interaction. In this direction, a group of octyl β-galactopyranosides and octyl N-acetyllactosaminides were described as substrates as well as

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• cases a switch of the binding site to the minor groove was reported. In an effort to influence DNA sequence-selective recognition by small molecules (MW <1000), our group prepared a series of phenanthridine derivatives with one or two nucleobases covalently attached at the 3 and/or 8 positions of the

• aromatic stacking and hydrogen-bonding interactions [73][74]. At variance to phenanthridinium–nucleobase conjugates (Scheme 23), which were not able to differentiate among mononucleotides, some bis-phenanthridinium–nucleobase conjugates provided a more convenient binding site for the nucleobase. For

• within the polynucleotide binding site. All 4,9-DAP derivatives also showed considerable antiproliferative activity, interestingly only 19 having strong, micromolar activity in vitro but negligible in vivo toxic effects in mice [97]. Strong fluorescence of 19 allowed monitoring of the very efficient

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• binding site of the ditopic guest ADAdim 4 and one binding site of a particular β-CD dimer, bearing a terephthalic acid linker, was independent of the number of binding sites, that is, no cooperative effect was observed and a supramolecular polymer was formed. ITC is one of the most interesting methods to

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• the methyl carbamate residue is the binding site. Despite the weak binding constants, the carbendazim water-solubility is increased but the effect remains low (1.9-fold compared to free carbendazim in the presence of 15 mM of β-CD). In 2012, Ge et al. proposed to use the HP-β-CD to enhance the

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• 6, 8 and 11 originates from a covalent binding of the halogenated analogues in the binding site of the target receptor [15]. The absence of antagonistic activity of these molecules in this biosensor however indicates that the reduction in QS activity results from the presence of the larger electron

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• -Et-S4U2) were added stepwise increasing amounts of a solution containing M.TaqI (10 µM), 36mer duplex with 2AP (200 nM) and a duplex 1I6S·2U4S or 1I6S-Et-S4U2 (400 nM) in the same buffers. The relative fluorescence intensity was determined after each addition. A model with one binding site and two

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland 10.3762/bjoc.10.225 Abstract An investigation of the interactions of two novel and several known DBTAA–adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is

• this study are long (<100 base pairs) synthetic polynucleotides poly dG–poly dC, poly dA–poly dT, poly dAdT–poly dAdT and poly rA–poly rU, each associated with specific structural properties of the minor/major groove as the anticipated binding site (APH, AP3, AP6 didn’t intercalate into ct-DNA [11

• intercalator). There are several possible explanations for the observed hypochromic effect, including the intramolecular stacking of DBTAA with adenine or the intermolecular stacking of two DBTAA chromophores within DNA/RNA grooves, a solvatochromic effect in the DNA/RNA binding site, and even a weak partial

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

• formation of large, monodisperse nanoparticle aggregates from galectin-3/glycodendrimer solutions is as follows. The glycodendrimer serves to nucleate the aggregation process through the specific binding of lactose into the carbohydrate binding site on galectin-3. Binding of the carbohydrate into the

• galectin-3 binding site must then be enabling protein–protein interactions. Some of these protein–protein interactions may occur because of intertwining of the N-terminal domains that are now in close proximity. However, protein–protein interactions using the carbohydrate recognition domains of galectin-3

Substitution effect and effect of axle’s flexibility at (pseudo-)rotaxanes

• Friedrich Malberg,
• Jan Gerit Brandenburg,
• Werner Reckien,
• Oldamur Hollóczki,
• Stefan Grimme and
• Barbara Kirchner

Beilstein J. Org. Chem. 2014, 10, 1299–1307, doi:10.3762/bjoc.10.131

• symmetric, and there are two recognition sites between axle and wheel, the latter sites strongly resemble each other in geometrical parameters. Thus, we only consider one binding site (isophtalic unit) with its hydrogen bonds. Note, that the hydrogen bond in the DB systems are more symmetrical than in SB

• systems. As the choice of the binding site is sort of arbitrary, we always choose the one with the shortest N–H···O distance. The full data can be found in the Supporting Information File 1. The hydrogen bonds listed in Table 3 fall in the range of 2.1 to 2.4 Å, and their angles range from 150 to 180

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• ., through molecular recognition of a preferred binding site [2][3][4][5], thereby ensuring the selectivity of a chemotherapeutic agent. Particularly common are side chains composed of deoxygenated sugars [6]. For example, the kigamicins are bacterial secondary metabolites isolated from Amicolatopsis sp. [7

Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• non-polar parts of the substrates, e.g., via attractive dispersive interactions, or provide steric hindrance that prevents substrates of a certain shape to be accommodated in the concave binding site of the templates. Since the 9,9’-spirobifluorene moiety provides such a rigid concave, non-polar

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• ) or hampering (negative allosteric cooperativity) the binding of another substrate at a second binding site. This powerful regulatory concept has become quite interesting in supramolecular chemistry, and the development of artificial receptor systems which can be controlled by allosteric effects comes

• well defined [Zn(1)2] complexes which, together with the NMR data, proof that zinc(II) ions are suitable to act as an effector for 1. Changing the substitution pattern to 6,6’ like in ligand 2, however, makes it impossible to form a 1:2 complex due to the steric crowding around the metal binding site

• sterically congested metal binding site of 3. Hence, we have to conclude that, unfortunately, we have not succeeded in finding a suitable effector for this ligand yet. Mixing of preformed complexes [Zn(22)]2+ and [Cu(22)]+ with 1 in a 1:1 ratio, however, afforded the desired heteroleptic complexes [Cu(22)(1

Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

• Midori A. Arai,
• Kyoko Uchida,
• Samir K. Sadhu,
• Firoj Ahmed and
• Masami Ishibashi

Beilstein J. Org. Chem. 2014, 10, 134–140, doi:10.3762/bjoc.10.10

• interacts with the Shh protein [12], and JK184 induces Hh inhibition through class IV alcohol dehydrogenase [13]. GANT-61 is an inhibitor, which disturbs GLIs binding to their binding site (GACCACCCA) in the promoter region of the target genes [14]. The AAA+ ATPase motor cytoplasmic dynein has been found to

• –515 amino chain, including the five Zn finger regions. Horseradish peroxidase (HRP)-conjugated streptavidin detected free “biotin-labeled GLI1-BS” (DNA containing GLI1 binding site; biotin-AGCTACCTGGGTGGTCTCTTCGA; the underlined 9 bps are a consensus sequence [30]; Figure 5, lane 1). After mixing with

• -CN-MS, 10 × 250 mm; MeCN/H2O 37:63, flow rate 2.0 mL/min, UV detection at 254 nm) to give compound 3 (1.7 mg, tR 24 min) and compound 1 (3.3 mg, tR 30 min). Electrophoretic mobility shift assay (EMSA) The double-stranded (ds) DNA fragments containing a GLI1 binding site (GLI1–BS) were prepared by

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• ) derivatives [12]. Conclusion In conclusion, compelling evidence suggests that 1 binds to an allotopic pocket of κ-OR, leaving the classical opiate binding site largely unoccupied. This suggests the possibility of creating bivalent derivatives by linking these scaffolds, with the potential for dramatic

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• reduction of Stat3 binding to all binding sites in the survivin promoter. ChIP experiments with primers comprising the suggested proximal NF-κB p65 binding site surrounding the transcriptional start site revealed a reduction of p65 binding after stimulation of NF-κB activity with 10 ng/mL TNF-α, 5 ng/mL IL

• bp). The primer sequences used for the NF-κB binding site within the survivin promoter were: NF-κB: forward primer, 5´-CTGCACGCGTTCTTTGA-3´; 5´-GCGGTGGTCCTTGAGA-3´ reverse primer (fragment size: 327 bp). The gapdh primer mixture was obtained from New England Biolabs, Frankfurt/M (SimpleChIP® Human

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• residues in the active site, the metal coordinating site and the substrate-binding site of these enzymes (Figure 1) [37][38]. After all, the interconversion between D-fructose and D-psicose catalyzed by DTEase enzymes is an equilibrium process, thus large scale and high yield production of D-psicose as

• biocatalysts for industrial-scale applications. The active site in D-psicose 3-epimerase (DPEase) in the presence of D-fructose, showing the metal coordinating site and the substrate-binding site. The purple ball indicates the manganese(II) ion coordinating with key amino acid residues (Glu150, Asp183, His209

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• bacterium. In 2001, the P. aeruginosa pilin O-linked glycans were found to be linear trisaccharides that are covalently attached to serine (Figure 1). The O-glycans contain a D-fucosamine residue at the protein-binding site. This unusual monosaccharide is not present in eukaryotes, and therefore may be used

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

• computer-aided docking studies to get an idea of their interactions with the carbohydrate-recognition domain (CRD) of the lectin. Docking of azobenzene mannobioside 2 into the carbohydrate binding site of FimH To visualise complexation of the (E)- and (Z)-isomers of azobenzene mannobioside 2 within the CRD

• rim of the carbohydrate binding site of this lectin. Before minimisation of the ligands, the bond angle of the N=N double bond of the azobenzene moiety was manually set as 180° for (E)-2 and as 90° for (Z)-2 [30]. Then docking was performed holding the FimH CRD fixed whereas the ligands were allowed

• portion is complexed in the carbohydrate binding site, the first mannoside does not add significantly to the affinity and this is in accordance with other studies on the complexation of oligosaccharides by FimH [11]. However, this mannose ring acts as a spacer moiety, sticking out straight from the CRD

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

• about the binding site, such as its density, orientation and position. Furthermore, the rigidity of the rods described above can contribute to overcoming the entropic penalty of flexible multivalent scaffolds, thus improving the overall activity of the ligands. Schematic depiction of (a) a rigid