Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• binding in solution and a further confirmation of the binding specificity obtained by the array experiments. We note that the functional activity of bacterially produced CMA1 indicates that potential modification by glycosylation is not required for ligand binding. Next, we set out to quantify the binding

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• of work. Then, the necessary feedback from the assays along with quite a few controls and further evaluations (i.e., from ligand binding thermodynamics, if the target is known, to cellular toxicity and all the way to early ADME) will also take some time. In other words, organic synthesis remains one

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• prediction of two C2 related, dominating binding sites on 14-3-3ζ that may bind to two of the supramolecular ligand molecules. Keywords: AIE luminophores; fluorescence emission; guanidiniocarbonyl-pyrrole; ligand binding; 14-3-3 protein; Introduction The 14-3-3 protein family was one of the first

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• complexes by Chan using complementary ligand binding [39], sometimes combined with conformational regulation [40], and of Newkome/Li [41] applying mainly geometric complementarity [42]. Clever utilized shape complementarity [21] for building heteroleptic palladium(II) cages whereas Crowley developed a

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• binding of biorecognition molecules on a PEG nanoparticle to its target only works when the PEG chain length is less than the polymer chain to which the ligand is attached. Otherwise, the long PEG chain will intercept ligand binding [50]. It is also reasonable to think that TPP is barely visible on the

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• thereby regulates genes that are required for queuosine biosynthesis [8][9][10][11][12][13][14][15][16]. The molecular mechanism behind is called riboswitching. For most riboswitches, ligand binding induces a structural change in the untranslated leader sequence of mRNA by formation (or disruption) of a

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• protein–ligand binding properties as well as biological activities of small molecules, potentially leading to dramatic increases in potency, and thus has been widely explored in drug discovery [54][55][56]. Late-stage C–H methylation has recently been investigated using iron and cobalt catalysts as

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• therapeutic potential. In addition, trans-4-phenyl-N,N-dimethyl-2-aminotetralin (trans-H2-PAT, 4, Figure 1) [6] has been determined to modulate tyrosine hydroxylase activity and dopamine synthesis in rodent forebrain and is also a ligand binding to histamine H1 receptors, and thus is a potentially useful

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• of the nature of the target proteins. CCR5, a cell surface receptor, is internalized upon ligand binding before recycling back to the cell surface or processed for degradation in the lysosome [34]. On the other hand, gp120 is a viral surface protein that is involved in viral entry through

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• enabled the direct calculation of most of the ligand binding constants. The superior capacity of 19F NMR to monitor binding events was also noted by Richards et al., when studying the interaction of human protein disulphide isomerase (hPDI) to Δ-somastatin [35]. In this work there was improved precision

• thermodynamic equilibrium binding constants (K) and kinetic rates of association (kon) and dissociation (koff) in protein–ligand binding events [37]. In order to achieve this, they analysed the binding of four different proline-rich peptides to a 5-FTrp-labelled Src homology 3 (SH3) recognition protein domain

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• other parameters such as binding-site size, cooperativity between ligands, ionic strength, the enthalpy of the DNA denaturation, and on the binding constant and enthalpy of the ligand binding at the melting temperature. However, the binding constant is determined at temperatures below Tm and the

• enthalpy of the ligand binding (ΔHb) is hardly accessible. Hence, we explain the very low ΔTm values for G4-DNA a2 in the presence of the ligands 4a–e with a very low affinity of these ligands at the melting temperature, which may be caused by the delicate, temperature-dependent equilibrium of the

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• multivalent ligands, like multi-armed GCP ligands with flexible scaffolds or nanoparticles, have been published yet. NMR spectroscopy is the ideal method to gain structural information and identify residues involved in ligand binding because it delivers single-residue resolution. It is also suitable to

• characterize the binding of ligands with moderate dissociation constants (KD) in the µM (up to mM) range, where the KDs for many first-generation supramolecular ligands lie. In the case of multiple ligand binding sites on one protein surface, NMR allows to identify the involved areas and provides an idea about

• at simple 1D proton spectra to study ligand binding to single amino acids or small peptides to introduce the basic principles and also briefly discuss ligand-detected NMR screening methods. Review One-dimensional 1H NMR spectra and basic principles to study ligand binding by NMR Simple one

A smart deoxyribozyme-based fluorescent sensor for in vitro detection of androgen receptor mRNA

• Ekaterina A. Bryushkova,
• Erik R. Gandalipov and
• Julia V. Nuzhina

Beilstein J. Org. Chem. 2020, 16, 1135–1141, doi:10.3762/bjoc.16.100

• the N-terminal domain (NTD). In vitro studies demonstrated that the progressive expansion of the length of the CAG repeat in NTD decreased its transactivation function. Exons 2 and 3 code the central DNA-binding domain and exons 4 to 8 code the C-terminal ligand-binding domain [14][15]. There are

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• million, most will be a consequence of extracting ≈35000 unique PMIDs. For BindingDB most of their 153000 unique structures are from the ≈200000 protein-ligand binding data points that were curated from 1,100 US Patents during 2019 (n.b., these will eventually be subsumed into ChEMBL release 26). We can

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• transfected with an expression plasmid containing the ligand-binding domain of human PPARα, -β/δ, and -γ fused to the GAL4 DNA-binding domain (pPPARα–GAL4, pPPARδ–GAL4, or pPPARγ–GAL4, 0.25 µg), a luciferase reporter plasmid 17m2G TATA Luc (p17m2G, 1 µg), and the pSEAP-control vector (1 µg, Clontech, CA, USA

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• cleaved diphosphate is shown in orange. (B) View of panel A rotated by 45°. For clarity, one monomer has been removed. The view is into the active site of CotB2. Conformational changes of CotB2 upon ligand binding. Superposition of CotB2’s open (teal), pre-catalytic (black, CotB2wt·Mg2+B·GGSDP), and fully

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• in their catalytic core domains, many isotype selective inhibitors have been developed in recent years [39][40][41][42][43][44][45]. In the case of Sirt2 it was shown that appropriate ligand binding can induce conformational changes of the enzyme, revealing a so-called selectivity pocket, which

• allows for isotype-specific interactions [46]. A recently developed fluorescence polarization (FP)-based assay enables mapping of ligand binding to this specific binding site [35]. For 2a an interaction with the selectivity pocket was already implied in the same work. Additionally performed docking

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• improve prospective antagonists and obtain a systematic tool for receptor investigation, spatial and temporal restriction of ligand binding and concomitant activity regulation is desirable. Fuelled by light, the growing field of photopharmacology provides a noninvasive method to trigger a drug’s

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• )–MgBr with many electrophiles. In most of the above trapping experiments, a slow disproportionation of t-BuCH=O was observed to generate t-BuCH2OH and t-BuCO2Li as side-products. The adduct 18 (Scheme 4) of fluoren-9-one (15) had again a triangular ligand-binding system at C-α, as shown by the

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• proteins consist of two domains: a larger N-terminal ligand-binding domain (LBD) connected to a smaller C-terminal DNA-binding domain (DBD). In 2006, the structure of the EHEC SdiA LBD was solved by NMR in the presence and absence of AHL and demonstrated increased folding and structure upon ligand binding

• ], Nguyen et al. observed that two residues in the ligand-binding pocket, Phe59 and Leu77, were moved inward toward the alkyl tail of 2, effectively closing the binding pocket relative to the “apo”-SdiA structure (bound to 1-octanoyl-rac-glycerol (23)). In Salmonella SdiA, these side chains are switched

• activity in the SdiA reporter assay, and recently reported data for LasR suggestive of a closed ligand-binding site for maximal activation [65]. All of the glycine ethyl ester head group compounds tested exhibited SdiA antagonism despite varying between a range of PHL- and PPHL-type tails with differing

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• did not have any effects at all on biofilm viable cells, 42 lead to remarkable results. In 2018, Kitao et al. solved the crystal structure for PqsR ligand binding domain in complex with M64 (42) with a resolution of 2.65 Å (Figure 19), unravelling the exact interactions of the compound with the

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• for the stronger binding of the ketone substrate to the Co-benzamide complex can be explained by the significant differences observed for the cobaltacycle ligand binding. The 5-membered cobaltacycle (with benzamide as the ligand) shows a significantly stronger cobalt–carbon interaction (Co·Clig

• in molecules (QTAIM) analysis using Multiwfn software [28] of the two intermediate structures, identifying the relevant parameters at the bond critical points (bcp) of interest. QTAIM analysis has been used previously in the field of transition metal organometallic complexes to understand ligand

• binding [29][30][31]. Analysis of the relative structural parameters for the two complexes (Table 1 and Figure 3) highlights an increase in bond lengths for the ketone substrate bound to the cobalt with the acetanilide ligand. The implied stronger cobalt to ketone interaction with the benzamide ligand is

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

• . Among the methods discussed, primary focus will be centered on the most frequently employed techniques, ECD and LD. Moreover, we will elaborate the interpretation of results not only for the most common DNA, RNA/ligand binding modes (intercalation, groove binding) but also for increasingly appearing

• addition, we will discuss the newest possibilities of computational analyses of the results as an outreach from the currently used empirical rules [6] for the determination of the ligand binding mode. 2. General aspects ECD and LD are based on the phenomenon of light absorption by one or more chromophores

• same samples (Figure 4). Of course, this fact has very important practical applications in monitoring the polynucleotide structure change caused by outer stimuli like ligand binding, pH changes, melting, etc. Intriguingly, most of the single-stranded (ss) polynucleotides, if long enough, also show some

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

• , respectively) to their holo forms excellently demonstrates the entropic costs generated by receptor flexibility. Whereas the binding site of the bacterial lectin G does not undergo conformational changes upon ligand binding (RMSD: 0.3 Å; Figure 8A), a conformational change involving a binding site loop allows

• intertwined domains (A, PDB: 4XOD). Upon ligand binding, FimH adopts the medium-affinity conformation (B, PDB: 4XOE), in which a loop (highlighted in green in the crystal structures) closes in the ligand, forming a deep and well-defined binding pocket. As urine begins to flow, the two domains are pulled apart

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• phosphodiesterase 10A [15], protease-activated receptor 1 [16], PIM-1/2 kinase [17], antagonists of the corticotropin releasing factor [18][19], vanilloid-1 receptor [20], and modulators for ligand binding to GABAA receptor [21]. As pyridazines are considered as privileged structures in drug design [22], we decided