Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• FRET probes (Figure 5) [14][25]. In the fit we used the associated phase angle (angle between the transition dipole moments of the donor and the acceptor) and the spectral overlap (JDA) as the fitting parameters. The phase angles for the tCO–tCnitro and the qAN1–qAnitro FRET pairs were 67° and 33

• measurements [62][63]. In conclusion, the FRETmatrix (base–base FRET) and Seidel’s methodology are in a way two extremes, firmly vs randomly oriented probes, both giving high control of the κ2 value which in turn facilitates high detail structure information determination. Studying nucleic acid conformation

• external probes as developed by Seidel et al. [4] comprise a highly interesting opportunity to investigate structure and dynamics of nucleic acid containing systems. Recent progress in the field of fluorescent base analogues also starts to close the gap in brightness to external fluorophores like Cy

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

• paramount interest because many biological processes, drugs and biochemical tools/probes rely on them [7][8]. Due to the possibly multifaceted nature of the complex formed between a small-molecule ligand and a large receptor (DNA/RNA), several complementary methods are needed for the accurate

• turbulent flow and 5000 rpm is an indicative figure. A necessary prerequisite for a macromolecule such as DNA is a minimum length of at least 1000 base pairs to be successfully oriented [10]. LD probes the orientation of base transition moments relative to the DNA helical axis. Thus, standard B-DNA whose

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• synthetic lipid A derivative had a bias towards MyD88- or TRIF-dependent immune responses [78]. 1.3. Synthesis of fluorescent-labeled lipid A analogues For studying the structural basis and the dynamics of TLR4-lipid A interplay, the application of labeled synthetic lipid A derivatives as versatile probes

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• [12][13], DNA fragment sizing [14][15], as reporter groups in hybridization probes [16][17][18][19][20][21][22][23], single DNA molecule fluorescence microscopy [24][25], gel staining [26], in real-time PCR analysis [27][28]) because of their excellent staining properties. Unsymmetrical cyanines have

• ]. Hybridization-sensitive fluorescent probes in which TO is tethered to a nucleic acid: DNA [22][23][33][34][35][36], RNA [20][36] or PNA [18][19][21][31]) strands have been constructed by several research groups (the Krull, Kubista, Seitz and Wagenknecht groups). The continued scientific and commercial interest

• in the preparation and application of cyanine dyes as bio-probes [37][38] and our research in this area [39][40][41] has led us to search for novel representatives of this interesting family of compounds. The main goal of the study described here was to investigate the influence of different halogen

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• activity [3][4]. Fluorinated amino acids can also be used as powerful 19F NMR probes for the study of protein–ligand interactions and enzymatic activities [5][6][7][8]. However, the development of fluorinated peptides as drug candidates seems to be largely under-exploited. Investigation on the influence of

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• anticancer drugs, antioxidants, or functional probes into the mitochondria [5][6][7][8]. Review 1. Synthesis of vinylphosphonium salts 1.1. Alkylation of phosphines with alkyl halides One of the most common methods for the preparation of vinylphosphonium salts 1 is the quaternization of vinylphosphines with

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• the reaction medium. The results suggest that 1 could be used as fluorophore in OFF–ON-type fluorogenic probes. Keywords: dipeptidyl peptidase-4; fluorogenic substrate; fluorometry; small fluorescent molecule; Introduction Fluorescent organic probes have become indispensable for bio-imaging or

• molecular imaging to visualize the presence of species such as particular enzymes and biologically important inorganic ions. In biomedicine, these probes are used for the detection of a wide range of significant biomarkers and are essential for the diagnosis of critical diseases [1][2][3]. Selective and

• accurate determinations of specific enzymes, including β-galactosidase [4][5][6], exoglycosidases [7], cyclooxygenases [8], and others [9][10][11][12][13], have been achieved using the OFF–ON-type fluorogenic probes with fluorescence that can be turned on by enzymatic transformations. These fluorescent

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• Organofluorine compounds now play an essential role in the development of new materials for solar cells [1][2][3], radiotracers for PET imaging [4], agrochemicals [5][6], sensitive chemical probes for 19F nuclear magnetic resonance investigation of biological experiments [7][8], and are most widely used in the

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• synthesis [3]. Pyrenyl derivatives have also attracted considerable attention as fluorescent probes in nucleic acid chemistry and closely related research areas. In particular the pyrene scaffold has been utilized for the construction of abiotic oligopyrenotides with nucleic acid-like structural properties

• detecting markers [14], as fluorescent DNA probes [15], non-covalent binders to canonical oligonucleotide templates [16], and antiviral agents [17][18]. Notably, pyrene excimer formation in DNA template assemblies is much less efficient than in normal pyrene conjugates due to the helical twist between

• better to single-stranded T10 and double-stranded (dA)10-T10. Confocal microscopy Over the past years, there has been an increased interest in the development of luminescent probes for bioimaging. In that respect, both metal-containing [35] as well as organic [36] luminophores were examined. We found

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• -emitting diodes (OLED), fluorophores, probes for ion sensing, functional polymers, and more recently also chromophores with nonlinear optical (NLO) activity. The latter property is mostly dictated by their conjugated character, electron-accepting behavior of the DPP scaffold, strong emissive character, and

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• of trifluoroethoxy-substituted phthalocyanines to biology Phthalocyanines are expected to be applied to medical fields [85][86] such as biological image probes and as agents for photodynamic therapy because of their excellent spectroscopic properties, allowing phthalocyanine to be a useful medical

• –vis spectrum, do not aggregate in solution. These dyes are expected to be developed into medical imaging probes. Phthalocyanine is expected to be used not only as a biological imaging agent but also in cancer treatment. Photodynamic therapy (PDT) is a laser cancer therapy that introduces organic dyes

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• ) [120] rescued L929 fibroblasts from mycolactone-promoted apoptosis while silencing FoxO3 by RNA interference was only partially protective. The latter finding might be explained by the compensating effects of other FoxO proteins. Two synthetic mycolactone-derived probes bearing a biotin tag as a

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• biological probes synthesized by automated synthesis by iterative coupling of different building blocks (colors). TBDPSE, tert-butyldiphenylsilylethyl; TMSE, trimethylsilylethyl. Adapted with permission from [37]; copyright 2015 American Association for the Advancement of Science. An example of a composition

Correlation of surface pressure and hue of planarizable push–pull chromophores at the air/water interface

• Frederik Neuhaus,
• Fabio Zobi,
• Gerald Brezesinski,
• Marta Dal Molin,
• Stefan Matile and
• Andreas Zumbuehl

Beilstein J. Org. Chem. 2017, 13, 1099–1105, doi:10.3762/bjoc.13.109

• fluorescent probes are an elegant solution to this problem but it requires first the establishment of a direct correlation between the membrane surface pressure and the induced color change of the probe. Here, we analyze planarizable dithienothiophene push–pull probes in a monolayer at the air/water interface

• using fluorescence microscopy, grazing-incidence angle X-ray diffraction, and infrared reflection–absorption spectroscopy. An increase of the lateral membrane pressure leads to a well-packed layer of the ‘flipper’ mechanophores and a clear change in hue above 18 mN/m. The fluorescent probes had no

• influence on the measured isotherm of the natural phospholipid DPPC suggesting that the flippers probe the lateral membrane pressure without physically changing it. This makes the flipper probes a truly useful addition to the membrane probe toolbox. Keywords: fluorescent probes; membrane biophysics

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• ][9]. In many cases, total synthesis is of critical importance to enhance the supply of these often scarce metabolites and even complex polyketides have been prepared on an industrial scale [10][11]. These natural products are also valuable molecular probes for the discovery and evaluation of novel

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• probing biological interactions and in biomedical applications [2][3][4][5][6]. Among these novel type of probes, luminescent semiconductors, quantum dots (QDs), which possess a narrow emission spectra and common excitation, superior photostability and electron density when compared to organic

• -octadecene) that could subsequently be functionalised with hydrophilic PEG-diamine, providing an amine functionality for conjugation with glucosamine, histidine, arginine and folate. The yellow/red emissive loaded-CDs were shown to be viable bioimaging probes in live cells, since their emission did not

• where found to localise in the cytoplasm and particularly around the nucleus. Due to the large amounts of internalisation a receptor-mediated endocytosis was proposed. The particles were used as fluorescent probes to target CD44 high expression in tumour cells, opening the door for these types of

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• -yl)-4-methylmorpholinium chloride (DMTMMCl), a coupling reagent frequently used in peptide synthesis. Malanga et al. recently reported on the preparation of xanthene-dye-appended CDs with the most commonly used fluorescent probes rhodamine and fluorescein (Flu, 1). The conjugation of the 6-monoamino

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• -synthesising enzymes ARTD1, ARTD2, ARTD5 and ARTD6. By varying the site and size of the NAD+ modification, suitable probes were identified for each enzyme. This report provides guidelines for choosing analogues for studying poly(ADP-ribose)-synthesising enzymes. Keywords: ARTD; click chemistry; NAD+; poly(ADP

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• 10.3762/bjoc.13.31 Abstract Recent advances in the use of flow chemistry with in-line and on-line analysis by NMR are presented. The use of macro- and microreactors, coupled with standard and custom made NMR probes involving microcoils, incorporated into high resolution and benchtop NMR instruments is

• optimization is discussed. Keywords: expert systems; flow chemistry; microcoil; NMR probes; Introduction New enabling technologies have facilitated the transition from traditional chemistry to a more automated approach that will be the chemistry of the 21st century [1][2]. The objective is that the reaction

• systems for the rapid analysis and optimization of reaction parameters and conditions. The use of this technique in mechanistic studies is also discussed. Review Commercial flow probes NMR spectroscopy is based on the absorption of radiofrequency radiation to produce absorption on the nuclear spin level

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• reduction of radical probes (no rearranged products formed from 25d,l,m) and deuterium-labelling experiments (no deuterium incorporation using THF-d8 and quenching with D2O) discard the possibility of a single-electron transfer pathway. Other reductions suggest a hydride addition with formation of an iminyl

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• as well as in the design of chemical probes to dissect glorin-mediated signaling pathways. Keywords: Dictyostelium; glorin; multicellularity; Polysphondylium; signaling molecules; social amoebae; Introduction The emergence of multicellularity from unicellular ancestors is considered a major

• is known about glorin’s biosynthesis, signaling pathways, or degradation. To facilitate further studies, our chemical route allows for a facile synthesis of glorin derivatives and glorin-based chemical probes. Here, we report the synthesis of glorin (1), as well as the novel synthetic analog

• allow for facile access to glorin derivatives required for structure–activity relationship studies. Eventually, these studies can lead to the construction of various chemical probes to identify the unknown glorin receptor. Syntheses of glorin and glorinamide (Scheme 1) started from commercially

Spectral and DFT studies of anion bound organic receptors: Time dependent studies and logic gate applications

• Srikala Pangannaya,
• Neethu Padinchare Purayil,
• Shweta Dabhi,
• Venu Mankad,
• Prafulla K. Jha,
• Satyam Shinde and
• Darshak R. Trivedi

Beilstein J. Org. Chem. 2017, 13, 222–238, doi:10.3762/bjoc.13.25

• ][24][25][26]. The choice of the appropriate detection technique is highly essential as it directly dictates the efficacy of the sensor. Anion binding through colorimetric probes comprising of a binding site and a signaling unit works in a coordinative way yielding an optical output visible to the

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• ]. Notably, the chromophore of the oxyanion-substituted quinolizinium derivative 2cB resembles the well-established solvatochromic pyridinium-N-phenolate betaine dyes that are employed as polarity probes [53]. Correspondingly, the derivative 2cB shows a similar positive solvatochromism, i.e., a blue shift of

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• traffic lights” [17][19][25] that are energy transfer-based nucleic acid probes that can be used in molecular beacons [26], especially for vesicular microRNA imaging in living cancer cells [27], and for siRNA transport imaging [28]. Donor and acceptor dyes are combined in an interstrand and diagonal

• /or fluorescence quantum yields. Thereby, improved fluorescent nucleic acid probes were elucidated that are suitable not only for nucleic acid imaging of living cells but additionally allow a two-color readout. Experimental Materials and methods. Chemicals and dry solvents were purchased from Aldrich

• energy transfer-based nucleic acid probes. Melting temperatures (Tm) and fluorescence quantum yields (ΦF) of singly modified DNA2aD1–DNA2rD4. Fluorescence intensity ratios (color contrast) C = IAc/IDo and fluorescence quantum yields ΦF of energy transfer pairs between dyes D1–D4 in DNA2a and DNA2r and

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• ) contrast agents and positron emission tomography (PET) probes for in vivo studies. Conclusion In this study, we described a novel preparation method for end-reactive PRXs using 3 as an axle polymer for the PRXs. The terminal 2-amino-3-phenylpropyl groups of 3 prevent the dethreading of α-CDs after end