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

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• tyrosine residues form the “tyrosine gate” [134]. By π–π stacking interactions with the aromatic tyrosine residues, monovalent α-mannose ligands containing hydrophobic aglycons, have shown increased binding affinities [128][135][136]. Employing multivalent ligands, the binding affinity to FimH could be

• ; in one of them the L-amino acids were replaced by D-amino acids (D-FD2, 51) to avoid proteolytic cleavage of the peptide construct [147]. Interestingly, it was found that the D-FD2 51 glycopeptide dendrimer showed a slightly weaker binding affinity to LecB, but the P. aeruginosa biofilm inhibitory

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• entire dataset, and to organize the results in such a way that areas on the protein surface exhibiting a strong binding affinity could be easily visualized by using standard display programs. In order to refine the docked structure of GSF a molecular dynamics (MD) simulation of the complex was performed

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• reaction mixture leads to the formation of α,β-unsaturated aldehydes. By branching, the avidity of glycans has been shown to increase, which is important for the binding affinity of lectins [56][57]. The chemically branched poly-LacNAc glycans may, moreover, serve as analogues to naturally occurring I

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• various degrees of binding affinity to the chimera. Based on the SI values, the α-mutants were classified into five interaction groups. As depicted in Figure 2 on the right-hand side, sequences with equal or slightly higher SI values compared to Acid-pp were classified as strong binders (only 22

• formation that are probably due to the destabilizing orientation of the polar hydroxyl group towards the hydrophobic core [21]. The clear decrease in binding affinity between chimera and Tyr-comprising mutants shows that the side chains at the artificial interface of the helix bundle experience an

• two Ile residues results in a medium binding affinity (Figure 4). This can be explained by the fact that, similarly to that of native coiled coils, the chimeric hydrophobic core is disrupted by excessively bulky side chains [22]. However, the preference for specific hydrophobic side chains in a and d

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• relationship has been developed for DAN·UG-based supramolecular-network polymer blends [40], and a redox-active eDAN unit was described wherein a >104-fold drop in binding affinity occurred upon reversible oxidation [41]. Herein, we extend the chemistry of the heterocyclic hydrogen bonding units (DAN and DeUG

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• -type 2-F-maltose isomers), which serve as internal standards, to rule out nonspecific binding and interactions, and thus increasing the reliability of this method. The 2-F-maltose reporter system was used to study the ligand binding affinity to MBP. “Fine tuning” by the regioselective fluorination of

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• ) methylene groups had a binding affinity for linear primary alkyl ammonium ions from n-BuNH3+ to n-HexNH3+. 3.2 Upper-rim derivatives Although the lower rim has many advantages as a binding site for guests, not least in the relative ease with which substituents can be attached, the upper rim can also

(How) does 1,3,5-triethylbenzene scaffolding work? Analyzing the abilities of 1,3,5-triethylbenzene- and 1,3,5-trimethylbenzene-based scaffolds to preorganize the binding elements of supramolecular hosts and to improve binding of targets

• Xing Wang and
• Fraser Hof

Beilstein J. Org. Chem. 2012, 8, 1–10, doi:10.3762/bjoc.8.1

• 1,3,5-triethylbenzene template directs the binding elements toward the same face of the central ring, hence increasing the binding affinity. At the same time the 1,3,5-trimethylbenzene scaffold, without steric-gearing effects, has also been found to improve the binding affinities of hosts compared to

• methyl groups, but the size of this advantage can be small and is dependent on the groups involved. Keywords: binding affinity; entropy; molecular recognition; scaffolds; supramolecular hosts; triethylbenzene; trimethylbenzene; Introduction Supramolecular hosts use arrays of multiple weak interactions

• different 1,3,5-triethylbenzene-based and analogous 1,3,5-trimethylbenzene-based tripodal hosts for their respective guests. These results are reported in Table 3. From this limited amount of literature data we see a range of binding-affinity differences for ethyl- and methyl-substituted hosts, which range

Ratiometric fluorescent probe for enantioselective detection of D-cysteine in aqueous solution

• Xiao-bo Zhou,
• Wing-Hong Chan,
• Albert W. M. Lee and
• Chi-Chung Yeung

Beilstein J. Org. Chem. 2011, 7, 1508–1515, doi:10.3762/bjoc.7.176

• cadmium complex (Cd2+–ACAQ) can induce a distinctive ratiometric fluorescence change characterized by the formation of an obvious isoemissive point at 450 nm (Figure 3b). We envisioned that the strong binding affinity of cysteine to Cd2+ perturbs its interaction with ACAQ in such a way that the ICT

• decreased. It is noteworthy that irrespective of the exact solvent composition of the aqueous solutions the binding affinity of the probe to Cys is fairly strong, as evidenced by the binding constants. On the other hand, the Job’s plot confirms the 1:1 binding stoichiometry of the sensing ensemble and Cys

• synergistic binding affinity of its carboxyl group to Cd2+–ACAQ. Such a proposition was supported by the observation that by converting the carboxyl group of cysteine into its methyl ester, the quenching ability of the derivative toward the probe was greatly reduced. To evaluate the binding mode of the Cd2

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• antimicrobial agents and the development of structurally new classes of antimicrobials with novel mechanisms of action as well as structural modifications to improve both their binding affinity and their spectrum of activity. One such strategy that has been pursued in recent years with increasing significance

Fluorometric recognition of both dihydrogen phosphate and iodide by a new flexible anthracene linked benzimidazolium-based receptor

• Kumaresh Ghosh and
• Debasis Kar

Beilstein J. Org. Chem. 2011, 7, 254–264, doi:10.3762/bjoc.7.34

• the key factors that regulate the PET to different extents. The binding affinity and selectivity of this simple fluororeceptor are associated with the combined effects of semi-rigid structures of receptor, charge-charge interactions, and the involvement of both N–H---O and C–H---O hydrogen bonds

pH-Responsive chromogenic-sensing molecule based on bis(indolyl)methene for the highly selective recognition of aspartate and glutamate

• Litao Wang,
• Xiaoming He,
• Yong Guo,
• Jian Xu and
• Shijun Shao

Beilstein J. Org. Chem. 2011, 7, 218–221, doi:10.3762/bjoc.7.29

• a basic H-bond acceptor moiety, could act not only as a color-reporting group but also as a binding affinity control group. The anion sensing properties of 1 based on acidic H-bond donor moiety have been studied previously in our laboratory [15]. The strong hydrogen bonding to, or protonation

An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids

• Xiao-bo Zhou,
• Yuk-Wang Yip,
• Wing-Hong Chan and
• Albert W. M. Lee

Beilstein J. Org. Chem. 2011, 7, 75–81, doi:10.3762/bjoc.7.11

• . The receptor 1 was fully characterized by 1H, 13C NMR, and high resolution mass spectral analysis. To evaluate the binding affinity of the synthetic host to dicarboxylate guest molecules, fluorometric titration experiments were carried out with the concentration of 1 fixed at 5.0 × 10−6 M in

• present in aspartates weakened their interaction with sensor 1, presumably due to non-bonding repulsions. In contrast, in comparison with the association constant between sensor 1 and glutarate, sensor 1 exhibited a stronger binding affinity to D- and L-glutamate (Table 2). Interestingly, a marginal

• aspartate and glutamate. Experimental findings indeed corroborated well with such a supposition. Compared with the interaction of the control compounds (i.e., succinate and glutarate), sensor 2 demonstrated a 3–10 fold stronger binding affinity with aspartate and glutamate, respectively. For instance, the

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• improved binding affinity. HIV reverse transcriptase inhibitor 22 and acid-stable fluorinated analogues 23–25. The F–C–C–O gauche effect influences the ring conformations of 23–25. Dihydroquinidine (26) and fluorinated analogues 27 and 28. Newman projections along the C9–C8 bonds of 27 and 28 show the