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

• nonavalent (86%) one. For this latter compound (11·HCl), IC50 = 179 μM was calculated [36]. This outcome is particularly desirable with multimeric iminosugars for increasing the overall binding affinity of weak inhibitors, as recently pointed out by Winum and Ulrich in a recent review [37]. It should also be

Size-controlled and redox-responsive supramolecular nanoparticles

• Raquel Mejia-Ariza,
• Gavin A. Kronig and
• Jurriaan Huskens

Beilstein J. Org. Chem. 2015, 11, 2388–2399, doi:10.3762/bjoc.11.260

• binding affinity. The positively charged Fc8-PAMAM multivalent guest was prepared according to a procedure developed in our group [27]. The positively charged Ad-terminated PAMAM (Ad8-PAMAM), used as a control, was prepared according to a literature procedure [11]. The neutral Fc-PEG stabilizer was

• of Ad is efficiently blocked by CD, which is in line with the approx. 30 times higher binding affinity of Ad (see above). Most importantly, this graph (Figure 5) confirms a 1:1 binding stoichiometry of the system. These results demonstrate that SNPs form optimally at a 1:1 stoichiometry at which all

• host–guest ratio at 1:1 and a high ionic strength of 0.2 M NaCl. Two different parameters were considered to study the effect of a stopper: length and binding affinity. The formation of SNPs was studied using constant concentrations of [CD] = 100 µM (CD is the number of moieties from CD-PEI) and [Fc

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• -solvent enhances the solubility of α-MGS with some effects on the binding affinity with β-CD, depending on the concentration employed. Keywords: α-mangostin; β-cyclodextrin; binary complex; inclusion complex; Introduction Solubilization of otherwise poorly soluble drugs under physiological conditions to

• additive contributions has potential to provide relationship between structure and binding affinity as well as the solvation effects. Theoretical basis of solvation free energy decomposition and the Free Energy Perturbation (FEP) formalism allowing additive for free-energy contributions arising from

• inclusion complex, as seen by a reduction in ΔGsolv at high ethanol percentages. In contrast, the entropies of all systems were likely similar (−T∆S of ≈13 kcal/mol). After combining the interaction energy (1), solvation (2) and entropy (3) terms, the binding affinity of the α-MGS/β-CD complexation at 0–60

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• levels in NPC1 fibroblasts, indicating the improvement of impaired autophagy by HP-β-CyD [28]. Therefore, it is necessary to investigate whether Lac-β-CyD can improve an autophagy function in NPC-like cells. Galactose density is one of the critical parameters of affinity to ASGPR. The binding affinity of

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• approximately 1.8 nm in diameter [69]. At first we expected that this series of triazole foldamers would be good hydrogen bonding acceptors. Intriguingly, the foldamers did not exhibit observable binding affinity to saccharides or amide derivatives even in less polar chloroform. Liyan designed different

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

• cyclized product. The cleavage of the acetate groups with sodium methoxide in methanol gave the glycophane (a glycophane is a hybrid of carbohydrate and cyclophane) 143 (27%, Scheme 21). The synthesis of fullerene-related molecules with high binding affinity and/or high selectivity is an active research

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• disclosed a study detailing the flow synthesis of a library of GABAA agonists which was linked to in-line frontal affinity chromatography (FAC) in order to directly generate binding affinity data for these new entities towards human serum albumin (HSA), a highly abundant protein in human blood plasma [110

• system. After establishing the void volume of this column, two different literature known marker compounds (diclofenac sodium and isoniazid) were used in order to calibrate the system based on their retention time which could be directly correlated to the protein binding affinity. Furthermore, as the

• µL, 67.5 µM) were passed through the binding assay column allowing quick determinations of their HSA binding affinity. This proof of concept study therefore marks one of the first published reports where flow chemical synthesis is combined with direct biological evaluation of new structures thus

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• of these findings into account, we conclude that the sulfonamide–zinc interaction dominates the binding affinity. The electronic differences of our azobenzene library is expressed by their absorption spectra (as an indicator for the electron richness of the azobenzene) or in their Hammett constants

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• ) scoring function and correlated with the binding affinity of the ligand for the FimH CRD. More negative scores indicate higher binding affinity than less negative values (Table 1). According to this docking procedure, Amadori products 9 and 10 have similar scores, which lie in the range of that for MeMan

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• intramolecular distance between TTF sidewalls and the strongest π-donor ability. Interaction with tetrafluoroquinodimethane (F4-TCNQ) The binding affinity of molecular clip 3 (5 × 10−4 M in CH2Cl2) was studied by a UV–visible titration with the electron acceptor F4-TCNQ (10−5 M in CH2Cl2). Addition of aliquots

Multivalency as a chemical organization and action principle

• Rainer Haag

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

• supramolecular designer systems [4][5]. The influence of spacer length and flexibility on the binding affinity of ligands [6] will be examined as well as the mechanical stability of complexes [7]. Furthermore, the Thematic Series covers the synthesis of various new glycoarchitectures for multivalent interactions

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

• determine the binding affinity, the enthalpic and entropic contributions to free binding energy, and the stoichiometry of binding for all peptide–polymer conjugates. Binding affinities of all multivalent ligands were in the µM range, strongly amplified compared to the monovalent ligand P1 with a KD > 1 mM

• sequences contained in numerous proteins including the core splicing protein SmB/B´and several splicing factors including splicing factor 3B4 (SF3B4) [16][17]. Recently, the enhanced binding affinity of bivalent and tetravalent peptide ligands to this protein was described suggesting that multivalent

• multivalent peptide–polymer conjugate to the tandem WW domain Binding studies with peptide–polymer conjugates were conducted employing isothermal titration calorimetry (ITC). This method enables the determination of the binding affinity of the multivalent ligands and elucidates the composition of the free

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

• binding affinity and derive general rules for the optimal ligand design. To this end, we first compare different polymeric models and determine the probability to simultaneously bind to two neighboring receptor binding pockets. In a second step the binding affinity of divalent ligands in terms of the IC50

• 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

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

• binding constants, as, for example, R2A2 shows the highest binding affinity, produces the greatest release of energy and has the smallest binding energy. With increasing peptide length, the binding affinity decreases, as does the release of energy, which is indicated by the increase in molar binding

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

• Erythrina cristagalli lectin (ECL) to proteins Gal-1 and Gal-3 as well as Gal-0 as a negative control. The three protein samples were each immobilized on a streptavidin-coated chip. Then, ECL was passed over the chip at different concentrations to determine the relative binding affinity for the immobilized

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• stable gradients of growth factors to regulate their bioavailability [11]. This matrix-immobilization of the factors might result in long-term binding to cell surface receptors, since the binding affinity of ECM-factors is relatively weak compared to growth factor receptor interactions [8]. Moreover, the

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

• located on apposing faces of the dimer (Figure 1). Although individual binding interactions with carbohydrates are weak [8], ligands for galectin-1 typically possess an array of carbohydrates to enhance the binding affinity [1][9][10]. Galectin-1 binding to carbohydrates cross-links adjacent

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

• events such as initial cell adhesion processes or pathogen invasion in host tissue. Nevertheless, ligand–receptor interactions are typically characterized by studying the binding affinity of freely dissolved ligands without surface anchorage. Typical assays in this context are “chip”-based methods like

• , steric shielding is not detected, which could explain the different outcome in terms of binding affinity per mannose unit in comparison to studies using inhibition/competition for binding affinity characterization [20][21][22]. Conclusion In this work, we successfully grafted three different carboxylic

• show that a high mannose concentration generally leads to increased adhesion energies. Although the mannose density was in principle sufficient to form multivalent binding with ConA receptors for all SCP systems, we did not observe an enhancement of binding affinity per mannose unit when increasing the

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

• ]. Three galactosylated DNA conjugates with different lengths were obtained and mixed with the corresponding half-slide complementary DNA to obtain supramolecular oligomers forming galactoside clusters. The different assemblies were tested for their binding affinity to the RCA120 lectin showing a

• flexibility of the linker introduced by an unpaired region. The same approach was also used to identify the optimal spatial arrangement for assemblies targeting RCA120 and L-selectin with mannose, LacNAc and sialyl Lewis X–PNA conjugates [45]. The highest binding affinity to RCA120 was obtained with a

• bivalent glycan assembly (LacNAc, presented at 140 Å distance) that was 70 times better than the monovalent assembly. Notably, the enhanced binding affinity for the divalent display is consistent with a distance of ca. 130 Å between the binding sites. It was also demonstrated that DNA-templated displays

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

• peptide ligand for the WW domains of FBP21 and were able to enhance the binding affinity by presenting it on a multivalent dendritic polyglycerol scaffold by a factor of ten in comparison to the monovalent ligand. However, given that on an average seven peptides are presented on the nanoparticle, this

• the interaction between hPG-peptide conjugate 2 and FBP21-tWW was measured by isothermal titration calorimetry (ITC) and compared to the KD of the interaction between the monovalent peptide and FBP21-tWW to analyze if multivalent display in form of the hPG-peptide conjugate 2 increases binding

• affinity. Results and Discussion Phage display In order to determine an optimal peptide sequence for a FBP21-tWW ligand, we conducted a phage display experiment for each of the two WW domains. Phages used in these experiments carried a randomized X9-peptide fused to phage coat protein VIII [16]. Enrichment

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• the corresponding TGA curve in Figure 4A and EDX (Figure 4C). Sulfonates have been described as ZnO binders before [47][48]. However, the binding affinity of 3-morpholinopropanesulfonate to ZnO NPs is low and most of the ligand is eliminated by washing following the immobilization. In contrast, TGA

Synthesis and surface grafting of a β-cyclodextrin dimer facilitating cooperative inclusion of 2,6-ANS

• Lars W. Städe,
• Thorbjørn T. Nielsen,
• Laurent Duroux,
• Reinhard Wimmer,
• Kyoko Shimizu and
• Kim L. Larsen

Beilstein J. Org. Chem. 2015, 11, 514–523, doi:10.3762/bjoc.11.58

• initial reports [1][2][3][4] of the cooperative effects exerted by β-cyclodextrin (β-CD) dimers, they have been suggested for a wide range of applications, for example, for catalysis [5][6] and photochemistry [7][8], as synthetic enzymes [5] and in general to obtain improved binding affinity (as compared

• accessibility for inclusion-complex formation [13]. The research presented here aims to bring the cooperative effects of β-CD dimers to solid silicon dioxide surfaces. Modification of these surfaces allows the introduction of the extraordinary binding affinity and selectivity of CD dimers to silicon wafer

• exception: the resonance at 3.46 ppm, these hydrogen atoms do not overlap with H-3 and H-5). In order to determine the binding affinity and to confirm the 1:1 stoichiometry of the complex, fluorescence titration experiments were conducted. Figure 6 shows the fluorescence spectra of 50 µM 2,6-ANS in PBS

A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

• Darinka Dzubiel,
• Heiko Ihmels,
• Mohamed M. A. Mahmoud and
• Laura Thomas

Beilstein J. Org. Chem. 2014, 10, 2963–2974, doi:10.3762/bjoc.10.314

• stabilize this DNA just moderately (ΔTm = ca. 3–6 °C). Although the cyanine derivatives 1d and 1e show the highest binding affinity towards ILPR-quadruplex, these ligands induce only a moderate shift of its melting temperature (Table 2). This apparent contradiction may be the result of different buffer

• with the telomeric quadruplex 22AG (Table 2). For example, the cyanine derivative 1e shows the most significant difference between the binding affinity towards ILPR and the telomeric quadruplex (a2: Kba2 = 1.7 × 107 M−1; 22AG: Kb22AG = 3.9 × 105 M−1). Although thiazole orange (6) has a relatively high

• terminal π-stacking [20], which is in agreement with the observed binding stoichiometry of 1:1 (Figure 7), the different composition of the loops in ILPR-quadruplex (ACA and TGT in ILPR versus TTA in telomeric quadruplex) may affect the binding affinity of ligands towards the ILPR-DNA. On the other hand

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

• impact on the binding affinity toward ds-DNA. The comparison of three substituents in 6-position, 4-N,N-diethylaminophenyl, phenyl (EB) and methyl, revealed that the first one exhibits the strongest DNA binding affinity and the strongest fluorescence enhancement. That was related to the twist angle in

• monomeric analogues) revealed significantly increased DNA-binding affinity and consequently enhanced telomerase and reverse transcriptase inhibition [69]. Conjugates of phenanthridine with other DNA and RNA active moieties Another common approach to increased selectivity of DNA- and RNA-targeting small

• much more dependent on the binding mode than on the substituents attached to the chromophore. However, by the rule of thumb, if phenanthridine substituents at 3,8-positions sterically allow the intercalation into ds-DNA or ds-RNA, than a binding affinity within the micromolar range could be expected

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• inclusion complex. The ligand binding mode and water accessibility, host–guest interaction, and binding free energy of the inclusion complex were analyzed. The MM-PBSA/GBSA and M06-2X/6-31G(d,p)//MM-PBSA/GBSA approaches were used to predict the binding affinity of fisetin/β-CD complexes. The M06-2X/6-31G(d