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

• interaction of proteins with their interaction partners, both biomolecules and synthetic ligands. In recent years, the focus in chemistry has kept expanding from targeting small binding pockets in proteins to recognizing patches on protein surfaces, mostly via supramolecular chemistry, with the goal to

• recent years, the focus of biochemical research and drug development has shifted from the inhibition of single enzymes to targeting protein-protein interactions [1][2], which play key roles in cellular function and dysfunction [3][4]. Enzymes usually bind their substrates in deep pockets with specific

• inhibition of potassium ion transport [39]. Another guanidinium-calixarene variant was designed to hold together the four tetramer subunits of a p53-R337H tumor suppressor mutant and thus restore tetramer stability [40]. Further examples for ligands targeting negatively charged patches on proteins include

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• spectroscopy methods (FDCD, CPL), the sensitivity of response is approaching the classical fluorimetric probes [14]. Our systematic work on aryl-guanidiniocarbonyl-pyrrole (GCP) derivatives characterised the GCP moiety as very useful building block in the design of new small molecules targeting DNA/RNA. The

• with diameter of 2 μm, or c) 500 nm. Done at pH 5, Na cacodylate buffer, I = 0.05 M. DNA-targeting roles of the structural components incorporated in the design of the novel small molecule. The NDI chromophore (DNA threading intercalator or possible groove binder) bearing two positive charges at

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• peptide chain and DNA/RNA interacting aromatic moiety, for instance peptide-based DNA/RNA-intercalators [1][2], as well as many DNA/RNA groove binding small molecules [3][4]. Inspired by these natural examples, the development of novel DNA/RNA targeting synthetic molecules has been in scientific focus for

• therefore adaptable for the design of FRET pairs with other dyes along the peptide backbone. Such amino acid construct would bring a novel functional property into peptide–multichromophore systems targeting DNA/RNA. For the design of our new constructs we noticed that the majority of DNA/RNA targeting NDIs

• peptide-backbone constructed multichromophores targeting FRET-based sensing [14][26][58]. For the application of here presented results in bioanalytical sciences or biologically relevant studies it will be necessary to further modify the presented compounds and precisely collect information about their

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• ]. Targeting more sustainable protocols, a manganese catalyst was selected to trigger the coupling between an aryldiazonium salt and simple (hetero)aryls. A unique reactivity was obtained under irradiation with blue LEDs and a continuous-flow process allowed achieving higher reactivity. Under the optimized

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• conditions [37]. This environmental pool of the infectious lifecycle stage makes even those individuals successfully treated by MDA schemes at risk of reinfection [38]. It has therefore been proposed that, as well as targeting improvements in sanitation to tackle this issue, an environmentally-acting, egg

• -targeting agent could play a complementary role to help break transmission [39]. The WHO has set a global target to eliminate morbidity due to soil-transmitted helminth disease in children by 2020 through the regular treatment of at least 75% of the children in endemic areas (an estimated total number of

• -Wolbachia treatments. These treatments target the bacterial symbiont Wolbachia which is essential for development, growth and survival of many filarial parasites. Targeting of Wolbachia with antibiotics has been shown to have curative efficacy against lymphatic filariasis [53] and importantly is safe to

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• differentiation, cell cycle progression and apoptosis by targeting both histone and non-histone proteins. The balance between acetylation and deacetylation is pivotal for typical cell function. Abnormal or increased HDAC expression has been reported in several human tumors and cancer cell lines [2]. As such, the

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

• ; photodimerization; photoswitches; Introduction The association of DNA-targeting drugs with nucleic acids [1][2][3][4][5][6][7][8] is considered one of the essential properties that determine their biological activity [9]. Specifically, a ligand may occupy particular binding sites of DNA or induce significant

• intrinsic toxicity of the employed drugs [11][12][13]. As a result, there is an urgent need for DNA-targeting chemotherapeutic reagents that can be activated with an external stimulus only at the desired point of action. In this context, light offers several distinct advantages to switch on the activity of

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

• . A major breakthrough concerning selective small DNA-targeting molecules was the use of pyrrole/imidazole hairpin polyamides. They are conceptually derived from the natural products netropsin and distamycin A, which selectively bind to particular sequences of the DNA duplex [2][3][4]. Covalent

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• helped to identify an antibody targeting the 5-methylthio-ᴅ-xylofuranose AM [7][14]. The Fujifilm SILVAMP TB LAM immunoassay chip provided a threefold higher sensitivity than Alere LF-LAM. Still, current technologies lack sensitivity and are limited to patients coinfected with HIV [7][10][15

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• in super-resolution microscopy [1][2][3][4][5][6][7][8] and as probes for targeting various biomolecules [9][10][11][12] or sensors for metal ions [13][14][15][16][17], pH [15], voltage [18] or metabolites [19][20][21][22]. Since our group is interested in synthesizing new tumor tracers for

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• on 5a were performed on an argon-purged, ca. 24 mM solution in acetone-d6. 1D NOE spectra were collected using 400 manually interleaved scans with a 4 s relaxation delay, targeting a single peak per experiment, in a manner similar to that previously reported [21] for photogenerated 4a,b

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• cyclohexenone bridges show good cycloreversion quantum yields of 0.20–0.32. The thermal stability of closed-ring isomers reveals half-lives of up to 20 days in solution at room temperature. The ligands were used to explore coordination chemistry with iron(II) targeting photoswitchable spin-crossover complexes

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• Glyco-DTE. More importantly, the β-ᴅ-galactoside cell-targeting moiety linked with Glyco-DTE forms a glyco-array on the MnO2 nanosheets that not only enhances the water solubility but also the cell targetability of the hybrid system towards HepG2 cell lines [25][26]. Therefore, by simply incorporating

• control reporter 8o with a PEG chain instead of the galactoside targeting group was also prepared. The detailed synthetic procedures and characterizations are given in Supporting Information File 1. Photochromic performances of Glyco-DTE The photoswitching performances of Glyco-DTE (1 × 10−5 mol/L) were

• presented undiscernible fluorescence signals, confirming again the selective targeting ability of Glyco-DTE. Next, the intracellular photoswitchable imaging experiment of Glyco-DTE in HepG2 cells was operated. Upon irradiation of alternate UV–vis light, an evident fluorescence ON/OFF cycle of HepG2 cells

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• of 0.34, comparable to other organelle targeting SiR derivatives and absorbs at 665 nm (εmax = 34 000 M−1cm−1) and emits at 681 nm (τ = 1.9 ns). Using colocalization experiments with MitoTracker® Green FM, we could prove the intrinsic targeting ability to mitochondria in two human cell lines (Pearson

• optical properties for medical and bioimaging. As a compound with intrinsic mitochondria targeting ability, the radiolabelled analogue can be applied in multimodal (PET/OI) imaging of mitochondria for diagnostic and therapeutic use in, e.g., cancer patients. Keywords: halogen-dance reaction

• rhodamines have been published. Dye 13 (Scheme 1, Table 1, entry 13) shows good water solubility, has a quantum yield of 0.12 and offers intrinsic targeting ability to lysosomes [35]. Pyridine silicon rhodamine 14 (Table 1, entry 14) has an improved quantum yield of 0.48 [32], presumably due to the

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

• structure–activity relationship studies towards novel antibiotics targeting 4-amino-4-deoxychorismate (ADC) synthase. Specifically, it is demonstrated that the synthetically challenging bicyclic motif is essential for activity towards methicillin-resistant Staphylococcus aureus (MRSA). Keywords

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• targeting steroid-fused pyrimidines, Boruah’s group developed a solid-phase MCR between 2-hydroxymethylene-3-ketosteroids, aromatic aldehydes and ammonium acetate [46]. As shown in Scheme 15, the reaction was carried out with steroid 49 and different aldehydes to furnish the set of compounds 50 in good to

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• respiratory depression. Indeed, anti-drug vaccines for individual conjugate vaccines of fentanyl and heroin have already exhibited protection in several animal models [3][4][5][6][7][8]. Antidrug vaccines targeting multiple, structurally distinct species are not common and have utilized two tactics: 1) mixing

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• into (E)-β-farnesene (19, I = 1460 (HP-5MS), Lit: I = 1459 (HP-5MS) [42]). The same outcome regarding the formation of (Z)-γ-bisabolene from (R)-NPP and FPP, but of 19 from (S)-NPP was recently also observed for BbS [13]. Targeting the stereochemical course of the 1,11-cyclisation of (R)-NPP to cation

• with (E)- and (Z)-(4-13C,4-2H)IPP, DMAPP, FPPS and HcS targeting the positions C-3 and C-7 (Figure S11, Supporting Information File 1), using published NMR data for 7 [44]. The stereochemical fate for the hydrogens at C-1 was then targeted by the incubation of (1R)- and (1S)-(1-13C,1-2H)FPP [28] with

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• strains, targeting both volatile and non-volatile compounds. The present paper will describe the discovery of one known and three new non-volatile terpenoids (Figure 1) that were isolated from liquid cultures of C. aegerita and their physicochemical and preliminary biological characterisation. Results and

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

• 1990s, the range of highly selective and potent drugs expanded based on various chemical structures. Nevertheless, on-off-targeting of a pharmacophore’s activity with high spatiotemporal resolution as provided by photopharmacology remains an unsolved challenge bearing additionally the opportunity for

• release [21][22]. Besides targeting of 5-HT3Rs for the treatment of psychiatric disorders, they are object to counteract postoperative nausea and chemo-/radiotherapy provoked emesis [26][27][28][29]. In the early 1990s, the first potent and selective 5-HT3 receptor antagonist ondansetron was initially

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• drug carriers, incorporating two different groups, for example a targeting unit and a prodrug, pseudoenantiomeric purity is not required, but the side-selective substitution has to be ensured. This has led us to develop a versatile and simple synthetic route towards difunctionalized β-CD, carrying non

• high selectivity towards the primary rim in monosubstitution of β-CD [22][23]. Our assumption was that targeting the disubstituted product with the same tosylating agent would preserve the side-selectivity and significantly reduce the number of possible regioisomers (6A,6B-, 6A,6C- and 6A,6D-ditosyl-β

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• ]. Herein, an indole-based macrocycle synthesis is reported in a one-pot fashion based on Ugi macrocyclization with readily available α,ω-amino acids. Moreover, in continuation of our efforts in the design and synthesis of macrocycles targeting the p53–MDM2 interaction demonstrating the potential of these

• postgenomic targets as it was demonstrated with the p53-MDM2 interaction. (A) Modeling of the macrocycle 2h (cyan sticks) and 2n (magenta sticks) into the MDM2 receptor (PDB ID: 1YCR); (B) 2D structure of 2h with the substituents targeting the subpockets of MDM2; (C) Analysis of the synthesized macrocycles

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• , IBI, and SIBIS multiblock copolymers, which include glassy, rubbery, and semicrystalline polymer segments and demonstrate peculiar mechanical behavior [57][58]. References [59] and [60] report on the preparation of fluorescent polymer nanoparticles for bioimaging and in vivo targeting of tumors and

• bioimaging and in vivo tumor targeting [60]. The multiblock copolymer capable of post-functionalization [76]. Multiblock copolymers synthesized by macromolecular cross metathesis. Changes in the DSC thermograms during MCM of PBD and polyesters (left) [84] and PNB–PCOE (right) mediated by Gr1 catalyst [89