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

• of base flipping to the overall binding affinity of the DNA adenine-N6 MTase from Thermus aquaticus (M.TaqI) as an example. Results Selective cross-linking of thionucleobase pairs in DNA by bis-alkylation with 1,2-diiodoethane Thionucleobases are excellent soft nucleophiles, and chemoselective

• association equilibrium with the dissociation constant KD,init, followed by flipping of the target base with the equilibrium constant Kflip (Figure 6a) [55][56][69]. The binding affinity of base-flipping enzymes is often determined using DNA with the fluorescent base analog 2-aminopurine (2AP) at the target

• (Kflip) to the overall observed binding affinity cannot be extracted from these data because the non-flipped and flipped enzyme complexes A and B (Figure 6) cannot be distinguished in a single binding experiment. Therefore the overall dissociation constant is given by (see Supporting Information File 1

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

• many groove binding molecules. The inability of the entire AP series to stabilize ds-DNA/RNA (Table 1), in combination with a considerable binding affinity (Table 2) gives rise to the question of the AP series binding mode. To shed more light on the unusual binding process of the AP dyes, it was

The effect of permodified cyclodextrins encapsulation on the photophysical properties of a polyfluorene with randomly distributed electron-donor and rotaxane electron-acceptor units

• Aurica Farcas,
• Ana-Maria Resmerita,
• Pierre-Henri Aubert,
• Flavian Farcas,
• Iuliana Stoica and
• Anton Airinei

Beilstein J. Org. Chem. 2014, 10, 2145–2156, doi:10.3762/bjoc.10.222

• –guest complexation stoichiometry. Thus, the Ks in CHCl3 was determined to be approximately 205 and 150 (±30) M−1, respectively (see the determined Ks of 1b in Figure 2). Concerning the binding affinity of molecule 1 to the TMS-β-CD and TMS-γ-CD cavities, it should be mentioned that the values toward

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• lipophilicity [1][2]. Moreover, incorporation of fluorine often results in an increase of the binding affinity of drug molecules to the target protein [1][2]. As a consequence, a considerable amount – approximately 20% – of all the pharmaceuticals being currently on the market contain at least one fluorine

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• the sensograms (Figure 3) showed a weak affinity of all calixarenes for Gal-3. However, the three synthetic molecules showed a very similar trend of Gal-3 binding affinity in three independent measurements (experiments A, B and C in Figure 4a). In particular, glycocalixarene 3 (cone structure, four

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• highly interesting to also modulate the binding affinity of a single molecule through a structural change as a response to an external stimulus, for example light. In order to gain such control over the binding affinity of glycooligomers towards specific lectins, a few studies have recently been

• –receptor binding and thus the resulting binding affinity. In order to determine the binding affinity of the precision glycooligomers to PA-IL, surface plasmon resonance (SPR) experiments were performed. At first, an inhibition/competition assay was carried out. The SPR chip was modified with a β-D

• could previously also show for glycooligomers binding to Concanavalin A (Con A) lectin receptor [7][10][11]. All multivalent glycooligomers show a decrease in IC50, i.e., an increase in binding affinity in comparison to the monovalent β-methyl galactoside. Overall, IC50 values are in the µM range, with

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 as previously postulated [18][31][36]. Ongoing studies on the aggregate stoichiometry should provide valuable insight on this matter. Overall, the results presented here indicate that clustering and aggregation events should be considered in addition to carbohydrate binding affinity for galectin-3

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• incapacity to form sufficient hydrogen bonds with the mannoside. Probably, the high propensity to form hydrogen bonds with water and the high flexibility of the arms of the receptor, are the main reasons that explain its low binding affinity in aqueous solvent. This work also presents a new application of

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• with different valency and alkyl spacer lengths by means of Cu(I)-catalysed azide–alkyne cycloadditions. Evaluation of these compounds as α-mannosidase inhibitors led to significant multivalent effects and further demonstrated the decisive influence of scaffold rigidity on binding affinity enhancements

• cyclopeptoid-based iminosugar clusters and their evaluation as α-mannosidase inhibitors. Modest but significant inhibitory multivalent effects were observed for most of the compounds evaluated. This study further highlights the decisive impact of the scaffold rigidity on binding affinity enhancements. In

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

• trace amounts of material, and can be used to explore competitive experiments that are difficult to perform using UV–vis or NMR spectroscopy. Results and Discussion Design and synthesis of the concave templates Ammonium ions exhibit strong binding affinity towards crown ether moieties. Hence, we decided

• interact via those interactions is weaker [33][34][35]. This observation perfectly agrees with the conclusion that the ester group gets into close contact with the non-polar parts of the templates, and thereby, contribute to the binding affinity by attractive dispersive interactions. Hence, we can conclude

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• have the drawbacks of carbohydrates such as low binding affinity or instability [4][5]. Many carbohydrates and their mimetics contain pyran rings, however, the corresponding ring-expanded compounds, oxepanes, have been investigated only in a limited number of studies. Several oxepane units can be found

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

• ]GTPγS assay. No compound caused detectable antagonism at 3 μM. Syntheses of heteromethylated derivatives of 1. b.r.s.m. = based on recovered starting material. Synthesis of (2-hydroxyethoxy)methyl ether 6. Binding affinity, potency and maximal response at κ-OR. Supporting Information Supporting

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• basicity of the secondary amine was thereby reduced by nearly two orders of magnitude, and this led to a marked improvement in bioavailability. Incidentally, it is also worthy of note that the bioavailability (and 5-HT2A binding affinity) could be further improved by the introduction of a second fluorine

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

• may lead to low to moderate yields and difficulties in product purification. Advancements in genomics and bioengineering can potentially solve this problem by improving the properties (activity, thermostability, or substrate-binding affinity) of existing enzymes or discovering new systems and robust

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• ]. Since single carbohydrate ligand–protein interactions are usually weak [4], several sugar ligands have to be introduced in order to achieve the desired biological effect [4]. This multivalent presentation of ligands then results in an increased binding affinity to the targeted protein receptors [4]. It

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• of other derivatives, was prepared through condensation of 4-iodoacetophenone (26) and indole-5-carboxaldehyde (27) to give 28, which was radiolabeled to give the target compound (Scheme 2D) [15]. The indolochalcone 21 showed good binding affinity for Aβ1-42 aggregates with a Ki < 10 nM. Replacement

• Aβ plaque binding affinity [19]. The [125I]-labeled methylamine aurone 31a presented great binding affinity to Aβ aggregates (Ki = 1.2 nM), better than all reported flavones to date. It also showed rapid brain uptake rate (3.17% ID/g at 2 min) and rapid clearance (0.24% ID/g at 60 min) [19]. The

• effect of the tertiary amine in this aurone scaffold was less pronounced than that seen with chalcones or flavones. The dimethylamine analogue of 31a had approximately six times weaker binding affinity, while the free amine analogue showed only two times weaker affinity. To further enhance the Aβ plaque

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

• to change their conformations under the influence of the force field. A FlexX scoring value has been attributed to each of the 30 obtained conformations (Table 3). This value correlates with the binding affinity of the ligand for the FimH CRD, more negative values suggesting higher binding affinity

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• comparable to the binding affinity of the known TcCYP51 inhibitor 5 [16]. 2-Pyridyl analogue 3 did not measurably bind TcCYP51 (KD > 2,000 nM, Table 1), whereas the corresponding 3-pyridyl congener (not shown) binds about 100-fold more weakly (KD ≈ 500 nM) than 4. These findings were thus consistent with our

Tricyclic flavonoids with 1,3-dithiolium substructure

• Lucian G. Bahrin,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2012, 8, 1999–2003, doi:10.3762/bjoc.8.226

• the binding affinity for estrogen receptor β. Further improvements in binding selectivity were obtained by combining the modifications performed on the C ring with modifications performed on the A ring, e.g. 2, Figure 1 [8]. Extracts from Hematoxylum campechianum and Caesalpinia sappan are known to be

Molecular solubilization of fullerene C₆₀ in water by γ-cyclodextrin thioethers

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1644–1651, doi:10.3762/bjoc.8.188

• between the anionic groups in between the two CD molecules was held responsible for the reduced binding affinity. Astonishingly, the amino derivative 1 also showed a high solubilization potential, which may originate from the addition of the amine to a double bond of C60, as was already observed by

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• obtained in azaMBH reactions of these three substrates with aromatic imines [30]. Matching the affinity data for Michael acceptors with MCA values we also find an inversion of Lewis basicity in that phosphane 89 has a larger MCA value but a lower binding affinity to the prototypical Michael acceptors

Cyclodextrin nanosponge-sensitized enantiodifferentiating photoisomerization of cyclooctene and 1,3-cyclooctadiene

• Wenting Liang,
• Cheng Yang,
• Masaki Nishijima,
• Gaku Fukuhara,
• Tadashi Mori,
• Andrea Mele,
• Franca Castiglione,
• Fabrizio Caldera,
• Francesco Trotta and
• Yoshihisa Inoue

Beilstein J. Org. Chem. 2012, 8, 1305–1311, doi:10.3762/bjoc.8.149

• the binding affinity. CDNSs 3–5 were dissolved in water to make aqueous solutions with concentrations of 45–60 μM in terms of the monomer unit, which were apparently clear at these concentrations but should be a suspension of swollen polymer. In view of the excess amount of PDA used in the preparation

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• favourable interactions of the nonpolar amino acid residues with the hydrophobic patches exhibited by the ligand, as well as high-energy water molecules being favourably displaced from the combining site. Binding affinity is therefore a result of combined enthalpic, entropic and solvation effects, frequently

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• carcinoma. In addition, a number of man-made inhibitors with a Smo binding affinity have been identified and reported [2][28][29][30][31][32][33][34], and some of them have entered phase I development. SAG is a synthetic Hh pathway agonist that directly targets Smo in a manner that antagonizes cyclopamine

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

• 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

• context of the chelate effect [21], and a number of theoretical models to treat multivalent receptor–ligand interactions have been developed [22][23][24][25][26][27]. A simple conclusion following from these analyses is that multimerization of monovalent ligands with enhanced binding affinity can lead to

• (WGA), besides other plant lectins such as Con A, has been intensively employed as a model lectin to study the influence of the structure of multivalent ligands on the binding affinity. WGA ligands of defined structure containing two to twelve GlcNAc residues obtained either by individual synthesis [28