Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• ligands; fluorescence; heterocycles; Pd-mediated couling reactions; quinolizinium; Introduction Polycyclic cationic hetarenes are a paradigm of DNA-binding ligands whose association with the nucleic acid may affect the biological activities of the DNA [1][2][3][4]. For example, a DNA-bound heterocyclic

• [14][15][16][17][18] and whose interaction with the nucleic acid may be used for fluorimetric detection of the latter [19][20]. To further exploit the DNA-binding properties of this specific class of cationic hetarenes, synthetic routes to novel derivatives with the desired substitution pattern and

• a hypochromic effect and red shift of the absorption bands as well as emission quenching or enhancement upon addition of the nucleic acid. Moreover, the binding constants Kb, as determined from the resulting binding isotherms, are in the same range (Kb = 2.0–22 × 104 M−1, Table 3) of known DNA

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• Melissa Meng Christian Ducho Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123 Saarbrücken, Germany 10.3762/bjoc.14.111 Abstract Their unique ability to selectively bind specific nucleic acid sequences makes oligonucleotides promising

• bioactive agents. However, modifications of the nucleic acid structure are an essential prerequisite for their application in vivo or even in cellulo. The oligoanionic backbone structure of oligonucleotides mainly hampers their ability to penetrate biological barriers such as cellular membranes. Hence

• linkages, with the nucleic acid mimic 'peptide nucleic acid' (PNA) [11][12][13] representing a striking example. Although the achiral PNA backbone is pronouncedly different from native nucleic acid structures, PNAs are capable of sequence-specific hybridization to native nucleic acids. However, their

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• -nucleic-acid-based, sequence-specific DNA-binding molecules. These conjugates could bind to four telomeric repeats with nanomolar dissociation constants, confirmed via SPR analysis. In the similar fashion, Nozeret et al. reported a series of nine fluorescent hairpin polyamides by attaching cyanine and

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• investigations into low temperature ice eutectic phases as the incubators of early life [120] and separately, the effects of high hydrostatic pressures upon ribozyme activities [121][122], it is surprising how little consideration has been given to the role of nucleic acid mechanochemistry under prebiotic

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• bind to mRNA targets through Watson–Crick base pairing and form a RNA/DNA duplex [4]. This can result in either mRNA cleavage mediated by RNase H or mRNA translational arrest through steric blocking. Another strategy for gene inhibition involves ribozymes [5] and DNAzymes [6], which are nucleic acid

• could be defined as caged oligonucleotides are transiently modified ONs with non-permanent chemical modifications (responsive units) that can be removed in response to appropriate stimuli, producing the native oligonucleotide. The aim of the prodrug strategy for nucleic acid therapeutic applications

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• to specific biomolecular targets, including nucleic acids as well as non-nucleic acid targets, such as proteins and small molecules, have applications in various important areas. These include diagnostics, drug development and as tools for studying biomolecular interactions in situ and in real time

• and biological stabilities in addition to their ability to bind to structured nucleic acid targets. In addition, the uncharged backbone of PNA allows for other unique designs that cannot be performed with oligonucleotides or analogues with negatively-charged backbones. This review aims to introduce

• proteins and other non-nucleic acid targets by employing aptamer technology [2]. However, ordinary fluorescent oligonucleotide probes generally show indistinguishable signals between the free and target-bound states. This means that additional treatments are required in order to separate the bound and

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

• acid bases inside the base-stack, base analogue donor and acceptor molecules complement external fluorophores like the Cy-, Alexa- and ATTO-dyes and enable detailed investigations of structure and dynamics of nucleic acid containing systems. The first base–base FRET pair, tCO–tCnitro, has recently been

• . Keywords: B-to-Z-DNA transition; fluorescent base analogues; FRET; netropsin; nucleic acid structure and dynamics; quadracyclic adenines; tricyclic cytosines; Z-DNA; Review Introduction The importance of nucleic acid structure and dynamics in the understanding of vital processes in living organisms has

• becomes a spectroscopic ruler. Such an assumption is often made, both correctly and incorrectly [8][9][10], for covalently attached external nucleic acid fluorophores like Cy-, Alexa- and ATTO-dyes. This provides a powerful means for measuring long distance ranges (typically 35–90 Å) in nucleic acid

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

• non-covalent complexes between nucleic acids and small molecules (ligands) is of a paramount significance to bioorganic research. Highly informative methods about nucleic acid/ligand complexes such as single crystal X-ray diffraction or NMR spectroscopy cannot be performed under biologically

• . The most relevant example here is that of an achiral ligand bound to a nucleic acid, yielding a so-called induced circular dichroism (ICD) whose sign and magnitude are determined by the binding geometry. In this case, the exciton coupling is said to be non-degenerate (Figure 3, bottom). It must be

• affected by other contributions, e.g., the non-degenerate coupling between different guanosine transitions, long-range couplings between distant guanosines, etc. More interestingly for our purpose, ECD is a useful method for probing conformational changes of nucleic acid upon ligand binding. Moreover, as

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

• valuable properties as nucleic acid stains have made these dyes an irreplaceable tool in the active and developing area of bioanalytical chemical research [9][10]. Cyanine dyes have found various bioanalytical applications as soluble DNA intercalators (e.g., in living cell imaging [11] and flow cytometry

• been conjugated to a variety of molecules, including peptides [29], proteins [30], DNA [17], and DNA analogues such as peptide nucleic acid (PNA) [16][31]. TO-based chromophores assembled as a structural scaffold inside nucleic acids (TO-tethered nucleic acids) have attracted considerable attention [32

• ]. 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

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

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

• yielded promising results. RNA capped with a locked nucleic acid (LNA)-modified dinucleotide cap analogue was translated 3-times more efficiently than regular m7G-capped RNA [64]. Additionally, RNA capped with the LNA cap analogue was found to be ≈1.6-fold more stable in a luciferase assay in cultured

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• AmCD–nucleic acid complexes were subjected to the heparin challenge test in order to assess their stability. Heparin is a highly negatively charged sulfated polysaccharide, which is used as a competitor polyanion. The results obtained (see Supporting Information File 1, Figure S2) show that

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

Beilstein J. Org. Chem. 2017, 13, 2671–2681, doi:10.3762/bjoc.13.265

• Jens Muller Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstraße 30, 48149 Münster, Germany 10.3762/bjoc.13.265 Abstract In nucleic acid chemistry, metal-mediated base pairs represent a versatile method for the site-specific introduction of

• Nucleic acids are increasingly being applied in areas beyond their original biological context, e.g., as a scaffold for the defined spatial arrangement of functional entities [1][2][3]. This often goes along with the formal substitution of a canonical nucleoside (or any other nucleic acid component) by an

• application in metal-mediated base pairing [6][7]. Structural analyses have shown that their formation is possible without major conformational changes of the nucleic acid [8], even though metal-modified nucleic acids may very well adopt non-helical topologies [9]. It is even possible to create DNA duplexes

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

• results substantiate further studies on pyrene–nucleobase conjugates as nucleic acid fluorescent probes and as cell imaging agents. Experimental General All preparations were carried out using standard Schlenk techniques. Chromatographic separations were carried out using silica gel 60 (Merck, 230–400

• 1555530 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/structures. Examples of pyrene derivatives with relevance to nucleic acid chemistry and structures of pyrenyl

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• are intrinsically sensitive to factors including protective groups on the glycan ring, reaction solvent, and additives present. As a result, further experimentation and analysis are needed to enable robust syntheses and achieve automation with comparable efficiencies of automated peptide and nucleic

• acid synthesis. With continuous development, the preactivation strategy will achieve wider applications in complex carbohydrate synthesis. Representative structures of products formed by the preactivation-based dehydrative glycosylation of glycosyl hemiacetal. Retrosynthetic analysis of pentasaccharide

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

• nucleic acid oligomers [53][54][55]. The presence of the mineral support is crucial here as it permits the preservation of the amphiphile bilayer structure during drying, thereby promoting the conversion of an “unreactive” organization (free floating vesicles and free monomers) into reactive chemical

• effect self-assembly [51]. Thus, mineral surfaces and porous formations could have been excellent media to foster the emergence of “self-contained”, dispersed chemical systems. Furthermore, mineral surfaces can serve as supports for chemical systems to undergo organization. The polymerization of nucleic

• acid monomers has been achieved in this manner: When amphiphile vesicles or liposomes are dried in the presence of solutes on a silicate support, a system of stacked lipid bilayers with intercalated solutes is formed [52]. In this arrangement, the nucleotides are optimally spaced to react and form

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

• devoted to control division processes. Challenge 3: characterizing the evolutionary dynamics of pre-Darwinian protocells. Rather than focusing on the reaction kinetics and evolutionary dynamics of populations of naked nucleic acid molecules (the core idea underlying the ‘RNA world’ hypothesis), or even

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• [14][15][16], drugs [17], cell organelle markers, for antibody, peptide and nucleic acid labelling [18][19][20], for pH [21], metal [22][23] and redox potential sensing (well-reviewed in Boens et al. [24]), as well as for the development of photodynamically active agents [25][26]. In this work, we

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

• corresponding polypeptide sequence is determined by a group of three bases in the corresponding section of the nucleic-acid chain [46]. However, the overlap between the sides of the consecutive pockets imposed an overlap in the corresponding coding nucleotides, telling that some sequences of amino acids should

• hydroxyl groups of ribose, resulting in a mixture of 2′,5′- and 3′,5′-phosphodiester bonds. By contrast, when peptides are present in the mixture, polymerisation is essentially happens through 3′,5′-phosphodiester bonds [52], stressing again the importance of peptides at the onset of prebiotic nucleic-acid

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

• of nucleic acid duplexes as well as that of phospholipids to form a bilayer membrane). On the other hand, even though the Second Law must always remain an inescapable constraint, a simple drift towards the equilibrium state is not sufficient to account for the evolutionary changes of life. More

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• /carbohydrate/nucleic acid derivatives [1][2]. One of the largest groups of bacterial secondary metabolites is polyketide from which a range of clinically used drugs have been developed. Polyketides still remain in the focus of drug development because of their structural complexity that can provide attractive

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

• cells. Keywords: dyes; fluorescence; nucleic acid; oligonucleotide; Introduction The “click”-type reactions [1], in particular the 1,3-dipolar cycloaddition between alkynes and azides (CuAAC) is a broadly applied strategy for postsynthetic oligonucleotide modification since both reactive groups are

• 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

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

• modifications result in numerous consequences. As earlier mentioned, CDs are used for numerous commercial applications. Therefore, the investigation of nucleic acid interactions (e.g., DNA or RNA) with various types of CDs is important to evaluate possible intracellular effects of CDs. The interactions between

• anthryl signals) in the presence of the 1-adamantanol guest. This concept could be very useful in nucleic acid reactions of medicinal and biotechnological importance for new drug delivery systems. Unfortunately, the binding constants between CDs and nucleic acids remain relatively modest and close to

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• analogue with a peptide backbone carrying nucleobases on its amino acid side chains [42] while Bradley et al. used the backbone of a peptide nucleic acid (PNA) with abasic sites which gives a reactive secondary amine for reversible attachment of aldehyde modified nucleobases [43]. Moreover, the DNA

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• are highly reactive compounds that are usually treated with alcohols or amines to give either a new carbonate or a carbamate-linked compound depending on the nucleophile. In one of our earlier reports, polycarbamate nucleic acids were synthesized from p-nitrophenyl carbonates with amines of nucleic

• acid derivatives [18]. Very recently, Hotha et al. utilized 1-ethynylcyclohexyl p-nitrophenyl carbonate to synthesize alkynyl glycosyl carbonate donors from hemiacetals [19]. Also, glycocarbamates [20] obtained from glycosyl p-nitrophenyl carbonates [21][22][23][24], were explored in studies of