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

• . Patch pipettes were filled with an internal solution containing (in mM): 135 potassium gluconate, 4 MgCl2, 10 HEPES, 4 Na2-ATP, 0.4 Na2-GTP, 10 Na2-phosphocreatine, pH 7.35. Good recordings were identified only when resting membrane potential (Rp) < −20 mV, holding current < 200 pA at −40 mV, and Rs 10

• an internal solution containing (in mM): 135 potassium gluconate, 4 MgCl2, 10 HEPES, 4 Na2-ATP, 0.4 Na2-GTP, 10 Na2-phosphocreatine, pH 7.35. The red fluorescent dye Alexa 594 (0.05 mM, ThermoFisher Scientific, Waltham, MA, USA) was added to visualize the morphology of the neurons. Normal ACSF was

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• sarcoplasmic reticulum (SR) within muscle cells. It transfers Ca2+ from the cytosol to the lumen of the SR at the expense of ATP hydrolysis. Specific inhibitors of SERCA are of significance to human health because of their well-documented value as research tools and their potential as novel anticancer agents

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• require less energy (ATP, redox power and/or photons) and can be supposedly operated at higher catalytic rates compared to natural carbon fixation. Accordingly, the synthetic CO2-fixation cycles should be able to convert more carbon dioxide with less energy in a given time and hence succeed natural

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• , acrylamide, N,N'-bisacrylamide, ATP, bromophenol blue, agarose, EDTA, IPTG, ampicillin, sodium dodecylsulfate, imidazole and DMF were purchased from Panreac (Spain, Barselona). Ethanol was purchased from MedChemProm. Coomassie Brilliant Blue R-250 was purchased from Bio-Rad (USA, CA). Bacto yeast extract

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• [10]. OATP2B1 transports its substrates, including estrone-sulfate in a sodium- and ATP-independent manner [11][12]. After entering the cells, estrone-3-sulfate is subjected to enzymatic conversions involving different cytosolic enzymes. The desulfation catalyzed by STS is followed by stereospecific

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• for nucleotides sensing through a dye replacement procedure. It is unusual that disubstituted macrocycles 10a,b bind more effectively a less charged adenosine 5'-diphosphate (ADP) than adenosine 5'-triphosphate (ATP). A simple colorimetric method based on polydiacetylene vesicles decorated with 10b

• was elaborated for the naked-eye detection of ADP with a detection limit of 0.5 mM. Keywords: ADP; amphiphile; ATP; calix[4]arene; CuAAC; eosin Y probe; molecular recognition; polydiacetylene; self-assembly; triazole; Introduction During the last two decades many researcher groups have paid much

• are very important as a universal energy source and as intracellular mediators in many biological processes [6]. In the cellular metabolism, adenosine 5'-triphosphate (ATP) is hydrolyzed to adenosine 5'-monophosphate (AMP) or adenosine 5'-diphosphate (ADP) by enzymes [7]. Thus, the receptors for

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• made to selectively recognize and detect these analytes, especially ATP using small-molecule fluorescent chemosensors. Despite the various solutions, the selective detection of ATP is still challenging due to the structural similarity of various nucleotides. In this paper, we report the conjugation of

• a uracil nucleobase to the known 4’-dimethylamino-hydroxyflavone fluorophore. Results: The complexation of this scaffold with ATP is already known. The complex is held together by stacking and electrostatic interactions. To achieve multi-point recognition, we designed the uracil-appended version of

• . Conclusions: The first, uracil-containing fluorescent ATP probe based on a hydroxyflavone fluorophore was synthesized and evaluated. A selective complexation with ATP was observed and a ratiometric response in the excitation spectrum. Keywords: ATP sensing; base-pairing; fluorescent probes; 3-hydroxyflavone

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

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

• analogue [50]. The problem of orientation is circumvented when GpppA cap analogues are used in combination with the T7 class II promotor phi2.5 which allows initiating RNA synthesis with ATP. Hence, GpppA- or m7GpppA-capped RNAs can be produced [51]. When the common GTP-initiating T7 class III promoter

• ] can be used. Primase incorporates cap analogues exclusively in their correct orientation. Normally, gene 4 primase from the T7 phage produces short RNAs with the sequence pppAC from a DNA template. Matsuo et al. observed that GpppA or m7GpppA can be incorporated as efficiently as ATP as the first

• double labeling of the mRNA cap with alkyne moieties could also be achieved based on a recently reported enzymatic cascade reaction [99]. In this system a Se-propargyl-modified AdoMet analogue (SeAdoYn [100]) was prepared enzymatically from the respective methionine analogue and ATP by a methionine

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• proton gradient, as well as its dissipation by the formation of ATP. The question as to whether, and if so what, alternative molecular assemblies could have been developed as primitive energy currency systems remains open and a topic of considerable debate. However, experiments have been carried out to

• reconstitute photosynthetic machinery in phospholipid liposomes [91][92] and polymersomes [93]. In these experiments, the use of photosensitizer triads or bacteriorhodopsin has allowed for the conversion of light energy into a proton gradient, which in turn could be utilized to power an ATP synthase to produce

• ATP from inorganic phosphate and ADP. In these systems, the “artificial” photosynthesis attained transduction levels that were comparable to those observed in cells, but in a completely artificial compartment. That such a complex dynamic system can be realized in artificial membranes is remarkable

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• , natural selection (NS) and evolutionary dynamics must come to the picture, too. Obviously, it is not legitimate to assume that the exquisite molecular machinery currently responsible for matter transport or energy transduction in cells (for example, ATP-synthases), even if they constitute a common feature

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• manipulation of the electro-chemical gradient built up between the inside and the outside of the cell (in particular with the fascinating nanomotor ATP synthase [14]). Membrane components age and waste away: This implies maintenance. Finally, there are specific needs to allow for division while the role of the

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• that of biochemical intermediates like ATP, requires a free energy potential exceeding a value of 150 kJ mol−1, equivalent to that of visible light [4][55][56]. Therefore, it turns out that considering the kinetic conditions for dynamic kinetic stability leads to the definition of conditions for the

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• elaboration of the aniline terminated surface (SAM 4-ATP) is the first step in creating SAMs bearing a sulfamide group, see Figure 1. For this purpose, 4-amino-thiophenol (4-ATP) was first adsorbed on gold surfaces. The aniline-terminated surface obtained can then react with ArSO2NHOSO2Ar (Ar = 4-MeC6H4 and 4

• after the different reaction steps. The values presented in Figure 1 display water contact angles for bare Au around 67 ± 2° as expected for a clean gold surface [41]. Upon 4-ATP adsorption the water contact angle decreases compared to the clean gold sample with a value of 54 ± 2° indicating the

• vibration is observed on the SAM PM-IRRAS spectra at 1153 cm−1. Therefore, by application of the strict IRRAS dipole selection rules, the SO2 group should be oriented parallel to the surface. The PM-IRRAS spectrum of 4-ATP on gold is shown in Figure 2b and is dominated by a band at 1627 cm−1 assigned to

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• fusion proteins were subjected to the ATP-[32P]pyrophosphate exchange assay. In this assay, the protein is incubated with a potential substrate, ATP and radioactive pyrophosphate. The reversible back exchange of [32P]pyrophosphate into ATP is quantified by scintillation counting after solid phase capture

• of ATP on activated charcoal [25]. Both recombinant AulA variants tested against the assumed substrate 3 led to similar turnover (Figure 3a) which demonstrates that the A1 domain is not essential for adenylation of 3 and PCP loading. Further functional characterization was carried out using the

• carrier protein; AT, acyl transferase; C, condensation; KR, ketoreductase; KS, ketosynthase; PCP, peptidyl carrier protein; TE, thioesterase. The gene aulD encodes a type II thioesterase. Testing of AulA (A1-A2-KR-PCP) and a truncated variant (A2-KR-PCP) in the ATP-[32P]pyrophosphate exchange assay using

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

• phosphate probe which are used to identify the binding sites for drug-like molecules and phosphorylated ligands (such as ATP) respectively [92]. The best ligand binding site identified in HIV-1 protease by SiteHound is shown in Figure 4. This ligand binding site is the known inhibitor binding site in HIV-1

• -throughput screening has been used to identify inhibitors of protein kinase CK2 targeting its ATP binding site [165]. CK2 is an important target in developing antitumor drugs. About 400,000 compounds have been screened, from which 12 hits were selected for evaluations using in vitro assays. Out of these hits

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• genetic molecule RNA (see below) and is also an important component of coenzymes (ATP, FAD and NAD). In 1992, Aoyama et al. reported on the selective complexation of pentoses and hexoses by β-CD [95]. Based on competitive inhibition of the 8-anilinonaphthalene-1-sulfonate binding followed by fluorescence

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• binding [43]. Additionally, phosphorylation may be found to direct desired behaviors in the currently intensively studied area of amyloid-based biomaterials. In this report we show the use of the negatively charged phosphate group to control the aggregation process. Using PKA and ATP (adenosine

• ATP was prepared and used to dissolve lyophilized KFM6. PKA is the most studied and structurally well-characterized protein kinase, and it is known to have relatively broad substrate specificity due to its roles in the regulation of energy metabolism, growth, signal transduction, and apoptosis of

• cells [50]. The serine/threonine kinase PKA uses ATP as phosphate donor. It has to be activated from its natural species with cAMP which leads to dissociation of PKA in two regular and two catalytic subunits [51]. We used the preactivated catalytic subunit of PKA to perform the reactions. The structural

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• into catalytic β-hairpins that serendipitously utilize aromatic interactions to maximize catalysis [37][38]. Along the way, we had some fun naming the hairpins that had the most interesting properties, including Chadtide – our first model system (after Chad Tatko) [16], Saratide – which binds ATP

• [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. (a) A clay model of our WKWK peptide (aka “Saratide”) made by Jes Park, a former graduate student in the group (reproduced with permission from Jessica Park). (b) Computational model of Saratide bound to ATP. (c) Inspiration from

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• peptidyl carrier protein (PCP) of the downstream NRPS module is loaded with an L-cysteine, which serves as a sulphur donor. From 177, sulphur is transferred by the NifS-like cysteine desulphurase TlmS to the tRNA-specific and adenosine triphosphate (ATP)-dependent 2-thiouridylase TlmJ, which is thereby

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• amount of RiPP chemical diversity is generated from cyclisation reactions, and the current mechanistic understanding of these reactions will be discussed here. These cyclisations involve a diverse array of chemical reactions, including 1,4-nucleophilic additions, [4 + 2] cycloadditions, ATP-dependent

• ” was a zinc-containing cyclase, and the “D-protein” possesses ATPase activity. The requirement for ATP turnover during cyclisation led to the hypothesis that the D-protein was a docking protein that regulates heterocyclase activity [33], while the presence of zinc in the C-protein pointed towards a

• catalytic role for this metal [33]. However, this role was later demonstrated to be structural rather than catalytic [34]. The Mitchell group showed [35] that the D-protein is actually directly involved in catalysis and uses ATP to activate the backbone amide bond for cyclodehydration, thus explaining the

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• derivatives 12 and 13. Phenylnannolone A was proven to restore daunorubicin sensitivity in cancer cells by inhibiting P-glycoprotein (P-gp), an ATP-binding cassette transporter (ABC transporter). In tumor cells, P-gp serves as an efflux transporter of drugs, ultimately leading to treatment failure [46]. Apart

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• electronic tongue and chemometrics were methods to differentiate ATP, GTP and AMP [92], phosphorylated peptides [93], as well as a technique to identify sweeteners in coffee and tea [94]. Each of these studies used combinatorial libraries of peptides around a preorganized scaffold or with a known targeting

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• used to prepare modified Pt electrodes with high stability and good qualitative sensing of ATP2− anions. It was supposed that the triethylene glycol domains in the block copolymers favor the amidoferrocene–ATP interactions by encapsulation. Astruc assumed that during the recognition process different H

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• number of carboxylases, phosphoanhydride bonds in ATP are hydrolysed to drive CO2 transformation through various molecular mechanisms. For example, biotin carboxylase catalysed reactions proceed through electrophilic activation of CO2 to carboxyphosphate to facilitate an attack by a nucleophile [28]. In

• all known natural CO2 fixation pathways, ATP and NADH or their equivalents are consumed in order to generate the intermediates that may feed into central metabolism [23]. This consumption is used as a measure of pathway efficiency for CO2-fixation, and pathways are considered most efficient when it is

• minimised [25][27]. By balancing thermodynamic feasibililty and a low requirement in NADH and ATP or equivalents, Milo and coworkers [25] were able to computationally predict the most efficient synthetic CO2 fixation pathways, using all known natural enzymes. Aqueous solubility and hydration of CO2 A