Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• lit-active photopharmaceuticals for the same binding site by a priori design. However, the potency of previous hemithioindigo photopharmaceuticals has not been optimal for their translation to other biological models. Results: Inspired by the structure of tubulin-inhibiting indanones, we created

• heterostilbenes that deliver green fluorescent protein (GFP)-orthogonal MT photocontrol [17]. However, in both azobenzene and heterostilbene scaffolds, the steric properties of the E- and Z-isomer are so different that the protein binding site shape determines that the Z-isomer (the lit-form) is the more

• cellulo [18]. We showed for the first time that the pseudosymmetry of hemithioindigos can be used to enable a priori design of HTI-based pharmacophores for a single binding site, with higher bioactivity as either the lit-form E- or the dark-form Z-isomer, just by changing substituent patterns, and

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• ligands 3a–c upon association with DNA resembled the ones observed for other styryl-substituted quinolizinium derivatives [62][63][64][65][66][67]. Accordingly, the emission enhancement most likely resulted from the accommodation of the ligand in the constrained binding site of the DNA, which led to a

• restricted conformational flexibility. As a result, conformational changes of the styryl substituent in the excited state that lead to radiationless deactivation in solution were significantly suppressed within the binding site so that emission became competitive. The DNA-binding properties of the ligands 3a

• relative to the ones of the DNA base pairs [75][76]. Considering a dipole moment of the donor–acceptor systems 3a–c along the long molecular axis, a binding mode in which the ligand is accommodated in the intercalation site with its long molecular axis perpendicular to the long axis of the binding site

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• binding site was monitored by emission spectroscopy. The addition of 2.3 equiv of E-P1 led to a displacement of 50% of TO (cf. Supporting Information File 3), which indicates only a weak binding of E-P1 because as a groove binder, the latter occupies more binding sites than TO. These data indicate that E

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• G reveals that the antibiotic is deeply buried inside the protein’s binding pocket and only a few sites of the molecule can possibly be modified without introducing steric clash with the binding site. Besides the methoxytryptophan which has been addressed by chemical synthesis, one appealing

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• interactions and binding energies of the selected compounds within the binding pocket of modeled proteins were found out by using MOE (2014.0901). MOE site finder was used to locate the binding site while default setting of the triangular matcher placement method in combination with GBVI/WSA ∆G, were used to

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• the neurotransmitter binding site, via a (still) mysterious mechanism [15][16]. Normally, TA-based drugs can activate nicotinic acetylcholine receptors, as shown, for example, by Trauner and co-workers [17] (azo-choline, Scheme 1). Here we explore the effects of addition of the tetrafluoro motif onto

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• calcium upon acting on the conformation of the adjacent binding site, rendering it a stronger or weaker binder. Photoswitching was studied in pseudo-physiological conditions (pH 7.2, [KCl] = 100 mM) and dissociation constants for azobenzene cis- and trans-isomers have been determined (0.230 μM and 0.102

• -withdrawing carbonyl function is generated from a secondary alcohol adjacent to the BAPTA binding site upon photoirradiation, which proved sufficient to lower the binding affinity 40-fold and liberate calcium in biological media [17]. This design was subsequently improved in a symmetrical variant and indeed a

• alternative approach to generate calcium release, where deforming an ion-binding site would render it less well-adapted to bind a guest. Photoisomerization of the azobenzene moiety has previously been successfully used to modulate the affinity of crown ethers [29], lariats [30], and foldamers [31] for various

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• substituent to the binding site of the receptor [24]. In order to obtain an efficacy photoswitching, we opted for replacing the biaryl moiety for an azobenzene in an azologization approach (Figure 1D) with the expectation that the isomerization of the azobenzene would provide changes in 3D shape that are

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• pair (pathway 2 in Figure S4, Supporting Information File 1). As all studied ternary complexes behaved similarly in the experiments, it can be stated that Me4N+ is located inside the cavity, while the PF6−, BF4− and I− anions reside in the exo-binding site. The binding efficiency of pyridine[4]arene

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• bulkier silver salt favored a mono-coordination on each binding site. Silver(I) complexes in solution Surprisingly, several batches of each complex 1a–d were compared by 1H NMR (CDCl3, 2 mM) (see Supporting Information File 1, Figure S9) and revealed slight variations in the chemical shifts that might

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

• 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

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• chemistry at the HF/6-31G*//HF/6-31G* level. Compound 1 molecule was manually docked into the SERCA binding site for thapsigargin using UCSF CHIMERA 1.10.2 (University of California, San Francisco) software by two approaches. In the first one, the molecule was docked so that the spatial orientation of the

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• liver [23]. The nucleotide-derived probe 5’-(para-fluorosulfonylbenzoyl)adenosine (5’-FSBA) was used for labelling the second nucleotide binding site, the adenine nucleotide regulatory site [24]. In addition, aryl fluorosulfates have also been widely applied as sustainable alternative to aryl halides in

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• substrate to the enzyme’s binding site could be identified by calculating the inherent structural mobility of the carbocation intermediates. This does involve the assumption that we can neglect the influence of changes in the interior structure of the enzyme as the reaction proceeds; however, based on the

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• prenyl donor [12]. This plasticity is due to the hydrophobic nature of the prenyl acceptor binding site and the fluctuations of the amino acids forming the cation shield, similarly to AmbP3. Comparison of the AmbP1 and AmbP3 amino acid sequences with other ABBA PTases The AmbP1 and AmbP3 amino acid

• shape of the substrate binding site. Conclusion The multiple structures of AmbP1 and AmbP3 with different substrate sets provide useful knowledge to understand the molecular basis of the promiscuous PTases. Their promiscuity is mainly caused by the hydrophobic binding pocket for the prenyl acceptor and

• useful catalysts that control the regiospecificity in an environmentally friendly manner. The information from their X-ray structures will contribute to future engineering of PTases. Furthermore, the structure of AmbP1 can serve as a model to alter the reaction through creating a metal binding site

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• conformations and with expected interaction points in the binding site, providing suitable docking scores (see Supporting Information File 1). The key interactions include a hydrogen bond to the backbone of Arg-45 and lipophilic interactions in the deep pocket defined by Phe-241 and Leu-34 (Figure 2). Our

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• is shown that the metal cations induce different pre-organization of the calixarene structure upon binding. The preferred binding site for the guest metal cations is the plane of the upper rim (with p-sulfonato groups), i.e., the sulfonate groups of hosts serve as anchoring points for the positively

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• with chromophore groups on their portals. However, the changes in the absorption spectra of these receptors upon anion binding were negligible since the groups on the portals were too distant from the anion binding site in the center of macrocycle. A different approach for the preparation of UV–vis

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• sites as it was observed for 5C2 and 5C4. The first GlcNAc moiety of 8C2 and 8C4 interacts with Asp29A, Asp129B, Ser148B and Tyr159B and nearly superimposes with GlcNAc in the WGA crystalline structure (site D2A1). The second GlcNAc moiety is at the vicinity of Ser19A and Tyr30A residues (A2 binding

• site), therefore mimicking the binding of two GlcNAc molecules on WGA. The distance between the two GlcNAc residues is 11–12 Å [41]. The alkyl chains (acetyl or butyl) fit in the non-polar environment provided by Trp150B and by Gly158B or by the acyl moiety of Lys33A (pose B, Figure 6). Nevertheless

Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes

• Krzysztof M. Zwoliński and
• Julita Eilmes

Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57

• differentiated Lewis-basic binding sites, however, from a broader perspective, the nature of the DBTAA binding site can be easily switched into a Lewis-acidic one after appropriate metal insertion (e.g., with zinc(II) ions) [33]. The crown-capped DBTAA’s were synthesized by refluxing 1,4,10-trioxa-7,13

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• . Keywords: binding site; DFT; enzyme mechanism; quantum chemical calculations; ThDP-dependent; Introduction Enzymes that depend on thiamin diphosphate (ThDP, Scheme 1) can be found in a wide range of metabolic pathways. Although they are known to catalyze the formation of C–N, C–O and C–S bonds, ThDP

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• database [82] was searched for structurally similar compounds leading to the identification of the meta-substituted tetrazole 33 (Figure 7), which was found to have a similar dissociation constant. Moreover, in order to predict the orientation of the fragments in the binding site, molecular docking of 33

• binding to the E. coli Zip A in the FtsZ binding site by means of 2D-HSQC NMR experiments and later submitted the selected compounds to cell division inhibition assays and MIC determination against a broad panel of bacterial strains which included S. aureus, B. subtilis, S. pneumoniae, H. influenzae, M

• –protein interaction, nonetheless considering the challenges involved in targeting PPIs, it is significant that the authors demonstrated by NMR that compounds from this library bind to ZipA at the FtsZ binding site and that small molecule disruptors of the ZipA/FtsZ interaction could inhibit cell division

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• modified by removal of the L-glutamic acid residue to give the pteroic acid moiety (Figure 2). The binding affinity of the modified folate is relatively weaker than folic acid [41]. The targeting ligand, pteroic acid, is covalently coupled to 8-aminocaprylic acid to separate the active binding site of