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

Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• proposed the compound to interact with ATP-binding sites [33], and it was subsequently used as a pharmacological tool for studying ATP and other nucleotide receptors. RB-2 has played a crucial role in identifying different purine receptor subtypes, since it was found to selectively block only certain

Synthesis of α,β-unsaturated esters via a chemo-enzymatic chain elongation approach by combining carboxylic acid reduction and Wittig reaction

• Yitao Duan,
• Peiyuan Yao,
• Yuncheng Du,
• Jinhui Feng,
• Qiaqing Wu and
• Dunming Zhu

Beilstein J. Org. Chem. 2015, 11, 2245–2251, doi:10.3762/bjoc.11.243

• reaction mechanism (post-translational phosphopantetheinylation, ATP, Mg2+, and NADPH as cofactors) [27][28][29][30]. As such, we initiated the search for new carboxylic acid reductases and the exploration of their potential as biocatalysts for the efficient bioreduction of carboxylic acids. Herein we

• was prepared and mixed with NADP+, GDH, glucose, ATP and carboxylic acid in Tris-HCl buffer. The reaction mixture was incubated at 25 °C for 16 h and extracted with ethyl acetate. The organic extract was concentrated to about 20 mL, and mixed with ethyl (triphenylphosphoranylidene)acetate and Na2CO3

• and aromatic acids of natural resources. However, the enzymatic reduction of carboxylic acids requires CoA, ATP and NADPH, and this still presents challenge for its application at large scale, which may be overcome by using the whole cell catalyst of the engineered enzyme production strain with

Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale

• Janne Weisell,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237

• Janne Weisell Jouko Vepsalainen Petri A. Turhanen University of Eastern Finland, School of Pharmacy, Biocenter Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland 10.3762/bjoc.11.237 Abstract Two strategies for the synthesis of the ATP (adenosine triphosphate) analogue ApppI [1-adenosin-5’-yl 3-(3

• characterized by 1H, 13C, 31P NMR and MS spectroscopical methods. Keywords: ApppI; ATP analogue; HPLC; purification; synthesis; Findings Bisphosphonates (BPs), which are stable analogues of pyrophosphate occurring in cells, have been used for decades for the treatment of many kinds of bone related diseases

• organic addition and substitution reactions [8]. In method B, the bis(tetrabutylammonium) salt of ATP was treated with isopentenyl tosylate to produce ApppI. The crude products were purified by an ion-pair chromatographical approach, based on the method first reported by Ryu and Scott [7], using

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• mechanism affects the VEGFR-2 signaling pathway by forming hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR-2 kinase unit [31]. Shankar and Srivastava et al. [32] treated PANC-1 xenograft mice with ellagic acid (7) and measured the expression of protein kinase B (Akt

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• was assessed using the ATP-based CellTiter-Glo® assay [50] on the human colon tumor cell line Caco-2. A first series of tests was performed in the relevant concentration range, i.e., 10× lower and up to about 10× above the clinically relevant concentration, namely 0.25 till 25 mg/mL of the polymer 5a

• generation of a luminescent signal proportional to the amount of ATP present, which is directly proportional to the number of cells in culture. The luminescence signal was measured in a plate reader (infinite M200, TECAN, Männedorf, Swizerland). 5a and DIMEB were each solved in standard basal medium (MEM) or

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• substrate. This limits the useful absorption range to ca. 350 to 400 nm for heterolysis by a primary photochemical pathway. Phosphates hold a central historic position in caged photochemistry through their cross-disciplinary significance in both biology and chemistry. Nucleotides (especially ATP, cAMP, and

• GTP) were among the first to be covalently bound to chromophores in a cage or PPG format that were demonstrably released upon photolysis. Benzoin caged cAMP and o-nitrophenethyl caged ATP, seminal examples of caged phosphates, are often the two classic caged biochemical substrates cited [6][7][8][9

• is reliable when extended to more complex phosphate leaving groups including nucleotides such as ATP and GTP and tyrosyl phosphates and thiophosphates [52][53][54][55]. The key comparisons for practical applications of photochemical deprotection are the maximum conversion which controls the chemical

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• using the α-D-pentofuranose-1-phosphates as glycosylating agents. The cascade synthesis involves a sequential conversion of D-pentoses into their 5-monophosphates catalyzed by the recombinant E. coli ribokinase (RK; ATP co-factor) [27], stereospecific isomerization of the 5-phosphates into α-D

• transformation of D-2FAra-5P into α-D-2FAra-1P as we have showed in our previous works [24][25][26][28]. This transformation was partly optimized by using variable concentrations of ATP, D-pentoses and biocatalysts. The results are shown in Table 4 and Figure 8. As expected, D-ribose is quickly transformed under

• -phosphate and 1-phosphate for the relevant E. coli enzymes were disclosed. The synthesis of clofarabine was optimized by using variable concentrations of ATP, 2-deoxy-2-fluoro-α-D-arabinose and biocatalysts. The results are shown in Table 4 and Figure 8. Conclusion In summary, the modified MacDonald′ method

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• residues of a substrate protein by transferring a phosphate group from ATP to the substrate protein [1][2][3]. This phosphorylation induces conformational changes of the substrate protein leading to initiation of a number of cellular events including signal transduction [4][5]. The human PKC enzyme

• natural product. Based on the information [48][49] that balanol binds to the ATP-docking site of protein kinase, all the three distinct domains present in the natural product such as the benzophenone core [50][51][52], the azepine core [53][54][55][56][57][58][59] and the p-hydroxybenzamide [60][61] unit

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• inhibitor) [3], R207910 (an ATP synthase inhibitor) [4] and moiramide B (a bacterial acetyl-CoA carboxylase inhibitor) [5]. Both natural 3-acyltetramic acids, for example streptolydigin 1a (bacterial RNA polymerase (RNAP) inhibitory activity) [6] and kibdelomycin 1b (bacterial type II topoisomerase

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• was carried out following standard procedures [21] with a radioactive 32P-ATP labeled probe. The probe was generated through PCR amplification using the aziA2 probe-F/aziA2 Probe R set of primers and following the same PCR condition as detailed above. Fermentation and analysis of secondary metabolites

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• “supercharged” mimics of pyrophosphoric acid capable of introducing additional anionic charge relative to simple methylenebisphosphonates when built into ATP and ApnA analogues [7][8][27][44]. They demonstrated that methylidynetrisphosphonic acid and especially its halogenated derivatives are key structure

• halomethylidynetrisphosphonic acids 43 and 44 is shown in Scheme 23 [7]. The tris(tributylammonium) salt of methylidynetrisphosphonic acid was transformed into an ADP analogue 45 and into an analogue of ATP 46 using the method of Poulter and the phosphoromorpholidate procedure of Khorana and Moffatt, respectively. Diadenosine

• of the lupine enzyme. Since the detection of levels of Fhit protein is an important problem relating to cancers, Fhit-selective inhibitors such as 47 and 48 can be valuable as Fhit diagnostics [8]. β,γ-Chlorophosphonomethylene–ATP, AdoPPCCl(P)P, is a weak antagonist at P2X2/3 receptors (IC50 about 10

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• clinical trials, has been the ATP-competitive inhibitors that bind to the N-terminal nucleotide binding pocket [4][5]. Hsp90 belongs to the family of GHKL (G = DNA gyrase subunit B; H = Hsp90; K = histidine kinases; L = MutL) ATPases, which is distinguished by a unique bent shape of its nucleotide binding

• pocket [6]. This distinctive shape has enabled for the design of highly selective ATP-competitive inhibitors of Hsp90. Through the efforts of multiple drug-discovery groups, many classes of inhibitors have been identified [3][5][7][8]. While much is known about the general types of structures that

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• active molecules to be synthesized with photochemically protecting groups at their active sites were nucleotides [1][2]. Two reports appeared in 1977 and 1978 describing the synthesis of ortho-nitrobenzyl derivatives of cyclic-AMP [1] and ATP [2]. The photolabile cAMP derivative was one member of a

• series of phosphate esters made as membrane permeable pronucleotides. Thus, this optical probe arose out of the context of the already developed prodrugs that used thermal chemistry for release of their latent cargo. In contrast, the photolabile ATP molecule was synthesized in a physiology department for

• rapid photoactivation of a particular enzyme, the Na,K-ATPase. It was the latter group that dubbed such photochemical probes “caged compounds”. This simple term has been adopted by biologists since that time [3][4][5][6][7][8][9], perhaps because the photolabile ATP compound was the one that was used in

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

• Laurie F. Mottram,
• Safiyyah Forbes,
• Brian D. Ackley and
• Blake R. Peterson

Beilstein J. Org. Chem. 2012, 8, 2156–2165, doi:10.3762/bjoc.8.243

• mitochondrial inner membranes (typically −120 to −180 mV, depending on cell type) [6][7][8][9]. This membrane potential is critical for ATP synthesis, and is generated by pumping of protons across the mitochondrial inner membrane by the respiratory chain. Many delocalized lipophilic cations preferentially

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• actin Actin was prepared from rabbit muscle as described previously [36]. The binding assay was used with the following modifications: Freshly prepared G-actin solution was diluted in Tris-ATP buffer (2 mM of Tris; 0.2 mM ATP; 0.1 mM CaCl2; 0.02% NaN3; pH 7.8) to an extinction of 0.28 at 290 nm (null

• room temperature the solution was filled up to ten volumes with Tris-ATP buffer and gently homogenized. Hydrophilic toxin derivatives were dissolved in potassium Tris-buffer (100 mM KCl, 1 mM Tris, pH 7.4). The concentration was determined spectrophotometrically at 300 nm (ε (300 nm) = 10100 M−1 cm−1

Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

• Torsten Dittrich,
• Nils Hanekop,
• Nacera Infed,
• Lutz Schmitt and
• Manfred Braun

Beilstein J. Org. Chem. 2012, 8, 1700–1704, doi:10.3762/bjoc.8.193

• 10.3762/bjoc.8.193 Abstract The inhibition of ABC (ATP binding cassette) transporters is considered a powerful tool to reverse multidrug resistance. Zosuquidar featuring a difluorocyclopropyl-annulated dibenzosuberyl moiety has been found to be an inhibitor of the P-glycoprotein, one of the best-studied

• “multidrug resistance”. Various transporters of the ATP-binding cassette family, so called ABC transporters, have been shown to be responsible for multidrug resistance [1]. Among these multidrug-resistance ABC transporters, the P-glycoprotein has been investigated most intensively [2]. As P-glycoprotein is

Thermodynamic and kinetic stabilization of divanadate in the monovanadate/divanadate equilibrium using a Zn-cyclene derivative: Towards a simple ATP synthase model

• Hanno Sell,
• Anika Gehl,
• Frank D. Sönnichsen and
• Rainer Herges

Beilstein J. Org. Chem. 2012, 8, 81–89, doi:10.3762/bjoc.8.8

• Hanno Sell Anika Gehl Frank D. Sonnichsen Rainer Herges Otto-Diels Institut für Organische Chemie, Christian-Albrechts-Universität zu Kiel, Otto-Hahn-Platz 4, 24418 Kiel, Germany 10.3762/bjoc.8.8 Abstract For the condensation of anions such as phosphate and ADP to form ATP and water, nature

• ; Introduction Driving endergonic reactions with external energy sources is one of the challenging and so far unsolved problems in supramolecular chemistry. The best known example in nature is probably the condensation of phosphate and ADP to ATP, driven by a proton gradient across a membrane [1]. There are a

• number of preconditions that have to be met for such an energy driven condensation of inorganic anions. At least three steps (four stages) are required (Figure 1): a) Moving both complexated anions together, b) bond formation (condensation), and c) product release/reactant binding. In the ATP synthase

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• studied, PatD is a single ATP-dependent enzyme not requiring an additional oxidase enzyme [60]. The PatG protease encoded by the cluster was shown to macrocyclize diverse substrates by a mechanism closely resembling the thioesterase-catalyzed chemistry of most NRPS systems [61]. Several related pathways

• Microcystis and Planktothrix [64][65]. Post-translational modification of microviridins is achieved by the activity of two closely related ATP grasp ligases, MdnB and MdnC (MvdC and D in Planktothrix). The enzymes introduce two ω-ester linkages between threonine and aspartate and serine and glutamate (MdnC

• MAA shinorine in Anabaena variabilis ATCC 29413: A dehydroquinase synthase homologue (DHQS), an O-methyl-transferase (O-MT), an ATP grasp ligase and an NRPS-like enzyme. Cloning of the entire gene cluster in E. coli led to the production of shinorine. The production of the intermediate 4-deoxygadusol