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

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• modulatory binding site in a different manner than 2 and its analogues [33]. Possible support for such a hypothesis can be seen in the different activity profiles of α,α-disubstituted glycine analogues of PLG and the corresponding α,α-disubstituted derivatives of lactam PLG peptidomimetic 2 [35]. In addition

• changes when these ligands bound to the allosteric binding site. This in turn produced different conformational effects at the orthosteric site where the dopamine receptor agonists bind. To test this hypothesis, the syntheses of β-dimethyl derivatives of 29a, 29b, 49a, and 49b, i.e., spiro-bicyclic

• analogues of 2 in which lipophilic moieties were incorporated into the structure to mimic the isobutyl side chain of the leucyl residue of PLG yielded analogues 10–12 (Figure 2) with increased activity, suggesting that the lipophilic side chain was enhancing the binding of the compounds to the PLG binding

Influence of cyclodextrin on the solubility and the polymerization of (meth)acrylated Triton^® X-100

• Melanie Kemnitz and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2176–2183, doi:10.3762/bjoc.8.245

• Triton® X-100 are reported in literature. In our previous paper, the coexistence of a 1:1 and 2:1 complex with an extraordinary high (K1 = 1.71 × 105 M−1) and a lower equilibrium constant (K2 = 260 M−1) was described [12]. Due to the fact that the tert-octyl group represents the preferred binding site of

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• the side chains in the small heterodet peptide ring are known to be involved in actin binding they were not used for derivatization. In the larger peptide ring, on the other hand, the dihydroxylated leucine moiety is juxtaposed to the actin binding site and thus appeared as most promising for

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• Based on the structure of the HIV-1 glycoprotein gp120 in complex with its cellular receptor CD4, we have designed and synthesized peptides that mimic the binding site of CD4 for gp120. The ability of these peptides to bind to gp120 can be strongly enhanced by increasing their conformational stability

• -amino acids. Keywords: biomimetic synthesis; CD4; HIV entry; peptide; protein binding site; Introduction Synthetic molecules that have the ability to mimic binding and/or functional sites of proteins are useful tools for exploring and modulating protein function, as they interfere with binding events

• protein binding site mimics. We have previously developed strategies for the design and generation of scaffolded and assembled peptides to generate protein binding site mimics [1]. The interaction of the HIV-1 envelope glycoprotein gp120 with its cellular receptor CD4 is the first step in the process of

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

• observed around a mannose surface density of 50%: if the mannose density is reduced even further, the average distance of the mannose units on the vesicle surface is larger than the binding site separation of ConA, and hence multivalent interaction is no longer observed. The average distance between two

• cyclodextrins at the vesicle surface is approximately 2.2 nm [30]. The distance between two mannose molecules is expected to be the same when using a maximum surface coverage of the cyclodextrin host surface with guest 1. The binding site separation for ConA is 3.6 to 4.9 nm [21][22], which roughly corresponds

• surface (dCH) exceeds the binding-site separation of ConA (dBS) [21]. However, the surface density of mannose also decreases if the guest molecule occupies two or even three cyclodextrin cavities but yet carries only one mannose unit (Figure 7). In the case of divalent guest 2 (with two adamantane units

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• the first strategy, because in structures such as (R)-9 the stereogenic center was rather close to the thiourea hydrogen bridge binding site. Scheme 3 summarizes our intended preparative approach towards (R)-9 via N-methyl-α-aminosulfoximine (R)-8, which unfortunately, remained unsuccessful. Heating

• likely serves as binding site for the substrate. Nevertheless, a remarkable enantiomeric ratio of 78:22 has already been achieved in the Biginelli reaction, which is known to be difficult to control. Thus, bringing the sulfonimidoyl group into closer proximity to the thiourea core might be beneficial for

• on the stereochemistry-determining path despite the fact that they were relatively close to the thiourea substrate binding site. Thus, reducing molecular flexibility by incorporation of plain arenes as linkers appears to be more important than conformational fixation through additional stereogenic