Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• general protocol for the use of ECD for the simultaneous determination of the binding mode and binding affinity of ligand/DNA complexes. In the light of the limitations listed above, here we would present an alternative approach, whereby an unknown DNA (or RNA)/ligand system is characterized primarily by

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• (Figure 1b). The most frequently employed approach here is to first synthesize citrate-stabilized AuNPs (Cit-AuNPs) [28], and then to replace the citrate ligands with the desired thiol-linked carbohydrate derivatives [29][30]. Ligand exchange on the AuNP surface is driven by the higher binding affinity of

Microfluidic radiosynthesis of [¹⁸F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors

• Thomas Lee Collier,
• Steven H. Liang,
• J. John Mann,
• Neil Vasdev and
• J. S. Dileep Kumar

Beilstein J. Org. Chem. 2017, 13, 2922–2927, doi:10.3762/bjoc.13.285

• [18F]FEMPT as an agonist PET ligand for 5-HT1AR. Results and Discussion Synthesis and binding affinity of FEMPT Desmethyl-MPT, the radiolabeling precursor, was synthesized as described previously [15]. The reference standard FEMPT (7) was synthesized in 70% by reacting desmethyl-MPT (6) with 1-bromo-2

• Psychoactive Drug Screening Program (NIMH-PDSP). FEMPT shows 0.2 nM binding affinity (Ki) to 5-HT1AR. The next closest bindings for MPT are Sigma2 PC12, H1, 5-HT7, and 5-HT1B (Table 1) and are >50 times higher than 5-HT1AR. The Ki values for several other brain receptors and transporters were low (0.1 to 10 μM

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• structure and the exact positioning of the triazole linkage, modified cap analogues varied largely with regard to their functionality in in vitro translational assays, binding affinity to eIF4E and resistance to the decapping enzyme DcpS. Best translational efficiencies similar to the standard cap were

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• obtain Tyr-Gly-Gly-ψ[(Z)-CF=CH]-Phe-Leu. The fluorinated Leu-enkephaline presented a 6-fold decreased binding affinity towards the DOPr receptor that the non-fluorinated analogue, showing that a hydrogen bond acceptor is necessary at this position of the peptide (Figure 6). The fluorinated peptide also

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• is the highly mannosylated glycoprotein uroplakin 1a (UPIa) [35][36]. The binding pocket of FimH accommodates a single α-D-mannose (1) with an extended hydrogen-bond network [37][38]. Accordingly, any modifications on the hydroxy groups of the mannose virtually abolish binding affinity [37][38][39

• structure based on a homologous MBP lectin domain from Rattus norvegicus and accordingly compared the measured binding affinity of rat MBP (Figure 1, F). Finally, a special case is the bacterial adhesin FimH, which can adopt three different affinity states (see below). For our discussion we focus

• ) forms a complex network of eight hydrogen bonds with ligand 2, one of them mediated by a conserved water [37]. Various approaches to realize binding affinity The immense variability of binding affinities among mannose-binding receptors is remarkable, albeit not surprising. While CRDs involved in the

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• ; Introduction The incorporation of unnatural amino acids into a peptide structure can potentially reduce conformational disorder and hence improve the binding affinity of the peptide for its biological target. For example, conformationally rigid amino acids such as 1 (Figure 1) have been shown to dramatically

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• synthetic, oxoisoaporphine-like analogues were found to have strong DNA binding affinity and therefore high cytotoxicity [5] as well as antiplasmodial activity [6]. Besides menisporphine (2), the related oxoisoaporphine alkaloids dauriporphine (3), 6-O-demethylmenisporphine (4), dauriporphinoline (5) and

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• for binding divalent metal cations and a modest increase in M2+ binding affinity correlated with increased alkycarboxylate tether length. Keywords: carboxylate ligand; merocyanine; metal binding; photochromism; spiropyran; Introduction Spiropyrans are a class of spiro-fused indolochromene (e.g

• ). The extension of this basic bidentate ligand with further substituents has been employed to generate structures with bespoke binding characteristics (e.g., metal ion specificity, control of complex stoichiometry, greater binding affinity) [17]. Typifying this approach, Natali et al. synthesised

• divalent over monovalent metal cations and a modest increase in M2+ binding affinity correlated with increasing alkycarboxylate tether length. This paper details a clear, effective protocol for the synthesis of N-alkylcarboxyspiropyrans and a thorough analysis of the effect of metal cations upon their

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• activity was shown by Poirier et al. [5]. They demonstrated that 13 epimers exhibit no substantial binding affinity for the estrogen receptor alpha and no uterotropic activity. Accordingly, the 13α-estrane core may serve as fundamental moiety for the design of hormonally inactive estrone derivatives

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• the bacterial recognition and bacterial infection inhibition. Three different morphologies of AuNPs (sphere, rod and star-like NPs) coated with galactose and mannose derivatives were employed for the quantification of their binding affinity to E. coli, suggesting that each shape could induce a

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• )anthraquinones with a series of cations demonstrated their high binding affinity to Cu2+, Al3+, and Cr3+. Keywords: amination; aminocholanes; bile acids; cation complexation; Cu-catalysis; diaminoanthraquinone; Pd-catalysis; Introduction Bile acids are known to ensure vital processes in vertebrate organisms

• was shown to decrease the yield of the Pd-catalyzed amination. This effect can be partially overridden by increasing concentrations of the reagents. The obtained bis(cholanylamino)anthraquinones demonstrated a high binding affinity to Cu2+, Al3+, and Cr3+. A tripodal molecular pocket (a) [12] or

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

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

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• . Stokmaier et al. revealed that the binding affinity of galactose to ASGPR elevated 100–1000 fold from mono- to triantennary galactose structures, probably due to clustering effects [22]. The dissociation constant of monosaccharide with ASGPR was 10–4 M, whereas those of triantennary and tetraantennary

• [15][16]. Therefore, the binding affinity of multi-Lac-β-CD (DSL5.6) to ASGPR is likely to be much higher than that of mono-Lac-β-CD. In fact, multi-Lac-β-CD (DSL5.6) has a quite low dissociation constant (2.6 × 10−8 M) with PNA, probably a result of its clustering effect in ASGPR recognition. The

• further elaborate studies to compare the binding affinity of multi-Lac-β-CD (DSL5.6) to PNA with mono-Lac-β-CD are necessary. In addition, to demonstrate the ASGPR-expressing cell-selective binding and cholesterol-lowering effects of multi-Lac-β-CD (DSL5.6), the comparative studies using ASGPR-negative

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• chloride to various primary and secondary amines. The authors propose that L1 binding with chloride results in a more electrophilic tritylated DMAP cation, and the binding affinity of the catalyst was found to correlate with the N-alkylation rate. Following the aforementioned studies, the Mancheno group

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• coordinates of the complex of the MI63-analogue with MDM2 [53][54]. The protein structure PDB ID 3LBL was chosen as the reference receptor because its ligand had high binding affinity and high resolution (1.6 Å). Docking studies were performed using AutoDock4.2 and both enantiomers of compounds 6a–f were

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• specific biological information as well. The BIND database contains protein complex information and biomolecular interactions [85]. BindingDB contains measured binding affinity information of proteins that are considered to be targets for drugs [86]. This database contains over one million binding data

• docking In molecular docking, how well a drug binds to its target is determined by the binding affinity prediction of the pose. This is done by scoring. Scoring is used to evaluate and rank the target–ligand complexes predicted by docking algorithms. Scoring functions are used in SBDD for scoring and

• scoring functions use evaluation criteria such as binding pose, binding affinity and ranking of true binders [114]. Wang et al. evaluated the performance of fourteen different scoring functions using 800 protein–ligand complexes in the PDBbind database [113]. The performance was evaluated by the predicted

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• squaraines can also be immobilized onto CDVs. For this purpose, the squaraines are equipped with two adamantane functions that bind into the cavities of cyclodextrin on the surface of the CDVs (Figure 1). The resulting divalent host–guest interaction should lead to a higher binding affinity of the squaraine

Robust C–C bonded porous networks with chemically designed functionalities for improved CO₂ capture from flue gas

• Damien Thirion,
• Joo S. Lee,
• Ercan Özdemir and
• Cafer T. Yavuz

Beilstein J. Org. Chem. 2016, 12, 2274–2279, doi:10.3762/bjoc.12.220

• pressure of CO2 in flue gas emission) and 273 K, the uptake is slightly higher than the starting COP-156. The chemisorptive behavior and stronger binding affinity is reflected in the higher Qst value of 49.9 kJ mol−1. The moderate binding energy is optimal for CO2 capture, as too strong binding requires

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• binding affinity and not the activity. Nevertheless, we focused on the most active compounds and determined the main interactions with the target protein that will be required for lead optimization. We first analysed compounds with the smallest substituent on the triazole nucleobase (derivatives 1n–q). As

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs. Keywords: binding affinity; click chemistry; Cu(I)-catalyzed azide–alkyne cycloaddition; pyrrole

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• triazolophane’s rigidity and that preorganization may be crucial for the large binding affinity. To test this idea, we examined the macrocyclic effect using an oligomer (Figure 8a) that folds up around chloride [17]. The affinity decreased by four orders of magnitude to ≈100 M−1, perfectly consistent with

• upon the correct estimate of the binding affinity. We originally missed a few features that impacted the accuracy of the binding constants. While these issues are quite common, their impact can be huge: our affinities had to be modified twice from Ka = 130,000 M−1 to 11,000,000 M−1 to 4,700,000 M−1 [6

• /acetonitrile). The aryl-triazole foldamer 24 formed a double helix with overall stability of β2 = 1012 M−2 [48]. Importantly, while we observed clear penalties to the binding affinity when we added extra water, we also saw that extra water increases the stability of the duplex. The analogy to hydrophobic

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• binding affinity [21], inhibition of hepatic cholesterol [22], inhibition of aldose reductase [23], antiproliferative [24], antiviral, cytotoxic [25], antifungal [26], anti-HIV [27][28][29] and antibacterial activity [30]. Although rare, there are a few natural products, for example, melanervin (5), a

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• group and the morpholine nitrogen. Though not observable in the solid state, this movement increases the binding affinity of linezolid under biological conditions. Due to our simulation this low energy minimum is populated 83% of the time at 310 K, dominating the recognition process. We repeated our

• contains a NH2 group that is able to form a weak H-bond, its amidic character and the lack of a chiral center leads to a side chain orientation parallel to the 1,2,4-oxadiazole ring, changing the overall binding mode in comparison with linezolid, and by this decreasing the overall binding affinity. Our

• the acetamidic arm and the G2540 phosphate group. Table 2 summarizes the results for the calculated relative binding energies. Due to our simulation, three among the 20 new linezolid analogues show a higher binding affinity in comparison with linezolid, which is not too bad for a first hit rate. In

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• interested in bisintercalators and the question of rigid vs flexible linkers? The triaminotriazine unit was designed to provide selective recognition of U–U or T–T mismatches, but on its own was viewed as unlikely to provide significant binding affinity because the hydrogen bonding simply involves replacing