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

• ligand may interfere with DNA–enzyme recognition events, which are essential for DNA-based cellular processes, e.g., gene replication or transcription [1]. To this end, it was shown that DNA-binding ligands may operate as chemotherapeutic anticancer, antiviral or antibacterial drugs, for example as

• [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

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

• relevance of enhanced nuclease stability and sequence-specific DNA binding. However, the gene-silencing effect could only be achieved if the modified oligonucleotide and the plasmid DNA were either mixed prior to cellular injection or if the oligonucleotide was injected first, pointing out a likely

• competition of the cationic antigene oligonucleotide with cellular histones for DNA binding [43]. Vasseur, Debart and co-workers have combined a variant of Letsinger's linkages with an α-configuration at the anomeric centers of antisense oligonucleotides [44][45]. They have found that such zwitterionic to

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

• play a significant role in target selectivity and specificity. Several focused reviews on small molecule DNA binding agents have been published in recent years. A few have updated the progresses made in disease specific DNA binders [14][15] while others have included class specific or site-specific DNA

• all DNA binding agents, this review article intends to provide a substantial coverage of new advancements made in the discovery of major leads in three most visited areas (groove recognition, intercalation and cross linking agents) of DNA recognition. 2. Minor groove binders (MGBs) DNA groove binding

• . However, these energetic costs are balanced and outweighed by favorable contributions from the hydrophobic transfer of drugs from solution to DNA-binding site [28][29]. Groove binding usually does not influence huge structural/conformational changes in the DNA duplex; this mode of binding may be

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• –platinum(II) complexes [94]. Both DNA binding and topoisomerase I inhibition studies proved that the coordination and stabilization of the quinone methide structure can effect marked changes in DNA reactivity. In a recent publication, 3-(aminomethyl)naphthoquinones were investigated from the point of view

Fluorogenic PNA probes

• Tirayut Vilaivan

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

• earliest PNA probes in this category are the so-called "light-up probes", which consist of a short single stranded PNA probe (ssPNA) linked to the DNA binding dye TO (Figure 18) at one end of the molecule, usually at the N-terminus, via a flexible linker [157]. The TO binds non-specifically with DNA

• the specificity due to the additional hydrogen-bonding interactions with the pairing G residue analogous to G-clamp phenoxazine. Moving the substituent to the meta-position, as in mmGuaPhpC, increased the binding affinity towards RNA while still maintaining good DNA binding [191]. When incorporated

• fluorescence dye and quencher to be in close proximity, resulting in quenching of the dye. Binding to the complementary DNA target opened the hairpin structure and restored the fluorescence. In Armitage’s design [42], the entire beacon was purely PNA, while in the Ortiz design [41], PNA was employed as the DNA

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

• distance window of opportunity than external fluorophores, and, thus, have the potential to facilitate better structure resolution. Netropsin DNA binding and the B-to-Z-DNA transition are examples of structure investigations that recently have been performed using base–base FRET and that are described here

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

• ], provided a step-by-step protocol to the measurement. Very recently, a similar tutorial was published for LD experiments [10], and also a general outline on how to interpret CD and LD results with respect to the most common ligand/DNA binding modes was summarized on a more comparative basis [6]. Within the

• is g ≈ 10−5, where g = ΔAbs/Abs = Δε/ε); the common approach of collecting a number of scans to improve the signal-to-noise ratio is time consuming. Thus, for the collection of titration data necessary to obtain an accurate binding isotherm (10–90% of complex formed, an excess of DNA binding sites

• aggregation types which could take place upon DNA/RNA binding. For instance, at an excess of ligand over dominant DNA binding site (minor groove), surplus ligand molecules can form simple dimers within the DNA minor groove [28], which at even higher excesses over DNA can change to different, larger aggregates

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

• the newly synthesized dyes as DNA fluorogenic binders. A further study of several aspects (including quantum chemical calculations and experimental studies on the DNA binding mechanism) should be carried out on these dyes in order to exploit in details their promising properties. Experimental

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• synthetic, oxoisoaporphine-like analogues were found to have strong DNA binding affinity and therefore high cytotoxicity [5] as well as antiplasmodial activity [6]. Besides menisporphine (2), the related oxoisoaporphine alkaloids dauriporphine (3), 6-O-demethylmenisporphine (4), dauriporphinoline (5) and

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• reaction scheme and rate equations could be approximated based on the predictability in the thermodynamics of DNA binding. In presence of an excess of the source ssDNA (denoted by G for “Grass”), traveling waves of a predator–prey molecular network (similar to the spatio-temporal patterns in the BZ

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

• considered the main source of cellular PAR [11]. ARTD1 and its closest relative ARTD2 comprise DNA-binding domains and their activity is stimulated by binding to different types of DNA breaks [12]. They fulfil functions in DNA repair, genome maintenance, transcription, and metabolic regulation [11][13]. 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

• derivatives may be modulated by supramolecular interactions. Considering the ability of this class of compounds to operate as DNA-binding ligands [56] or water-soluble chemosensors [57], we anticipate that the combination of these properties with the potential for modulation by host–guest assembly may widen

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

• the mutagenic DNA binding, is then set up stereospecifically by the versiconal cyclase, which accepts both enantiomers (2’R and 2’S) of versiconal (105) [96][108]. Heterologous expression and characterisation by Townsend and co-workers revealed that the versicolorin B synthase (VBS) does not require

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• (>10–12 base pairs) that results in promiscuous binding events. To resolve the mentioned problems, a chemical conjugation of several DNA-binding ligands (TFOs, MGBs) was used in order to profit from useful properties of both components in the resulting TFO-MGB conjugates [10][11] and MGB tandems [12

• succeeded to obtain a conjugate of two polyamides by template-directed synthesis on the adjacent sequences of a target DNA fragment using the Huisgen 1,3-cycloaddition reaction even without copper catalysis [39]. The rational for this type of synthesis was to find an optimal orientation of two DNA-binding

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• , for example, the ends of DNA double helices, replication forks, or abasic sites. My original research proposal was submitted August 16, 1983 and was entitled “Synthesis of a Rigid ‘Molecular Tweezer’ with Novel DNA Binding Potential.” The name “molecular tweezer” was inspired by Howard Whitlock’s 1978

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• be suggested as being partly responsible for the activity. Furthermore, cytotoxic modes of action of pyridoacridine alkaloids include DNA-binding properties, topoisomerase (TOPO) inhibition [91] or the production of reactive oxygen species (ROS) [92][93]. It was shown that planar iminoquinone

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• His may have a synergistic effect on siRNA transfection. Moreover, the biocompatible nature of the amino acids can possibly decrease the cytotoxicity of the resulting vectors. Furthermore, Arg and His groups interact in histones, as natural DNA binding proteins, via their positive residues with the

A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

• Darinka Dzubiel,
• Heiko Ihmels,
• Mohamed M. A. Mahmoud and
• Laura Thomas

Beilstein J. Org. Chem. 2014, 10, 2963–2974, doi:10.3762/bjoc.10.314

• DNA structures [15]. It has been demonstrated throughout the last decade that quadruplex DNA-binding ligands have a large potential to increase its stability towards unfolding and to influence the equilibrium between different quadruplex forms by stabilizing one particular quadruplex conformation [16

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• derivatives are one of the most intensively studied families of biologically active compounds with efficient DNA binding capability. Attracting attention since DNA structure discovery (1960s), they were early recognized as a symbol of DNA intercalative binding, for many decades applied as gold-standard DNA

• quenching [54][55]. Taking into account the research results of several other groups, a general rule could be drawn that phenanthridines with no amino groups yield strong fluorescence in water but emission is totally quenched by DNA binding; one amino group at (usually) position 8 results in only a small

• fluorescence change in the complex with DNA, while two amino groups in 3,8-position result in a weak fluorescence with strong emission increase upon DNA binding [52][53][56]. A pronounced influence of the substituent at phenanthridine position 6 on the optical properties of the chromophore also had significant

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• interstrand cross-linked DNA is an interesting tool to study DNA binding proteins that locally open up the DNA duplex by flipping single bases out of the DNA helix or melting whole stretches of base pairs to perform their function. The ideal DNA cross-link to study protein–DNA interactions should be specific

• -modifying enzyme no matter what target base specificity it possesses. While different linker geometries might work for different DNA-binding proteins, the ethyene-linked thiobase pairs offer the advantage of a very short linker with little steric demand for studying DNA-opening enzymes. The cross-linked

• helicases, which locally separate the two DNA strands, are important to enable vital cellular processes like DNA replication, DNA repair, chromatin remodeling and telomere maintenance [78][79][80][81]. Cross-linked DNA will not only provide a useful tool to study DNA binding and base flipping thermodynamics

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support

• visible for ct-DNA (58% AT base pairs), which confirms that any AT-DNA sequence even in mixed polynucleotides will give a characteristic ICD pattern. Structure–activity relations of DBTAA–adenine conjugates in AT-DNA binding Despite the results described above, it is still not clear whether the origin of

• AP3/AP3am cannot form efficient intramolecular stacks because the AP3/AP3am propyl linker is too short to allow adenine to stack above the DBTAA moiety (Figure 4 lower left). Thus, it can be expected that, given an excess of AP3 over DNA binding sites (r > 0.3), two AP3-DBTAA moieties will form π–π

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• fashion. PNA–DNA duplexes have different structural morphology and electrostatic potential surfaces from DNA–DNA duplexes and therefore they are interacting differently with DNA-binding dyes [23][24][25]. We had recently introduced a new conformationally constrained pyrrolidinyl PNA known as acpcPNA that

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• oligonucleotides we have summarized the ΔTm/modification data for RNA and DNA binding of the four modifications within the same sequence context for which data was available (Table 3). From the data it becomes evident that there is no clear correlation between torsion angle γ and affinity. For example bcen-T

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• -SREAKKQVEKAL-KQLEDKVQ) consists of a short C-terminal peptide from the M protein (in bold), placed within a sequence derived from the GCN4 leucine zipper DNA binding protein of yeast, which is known to promote an α-helical structure [33]. This chimeric peptide has been shown to elicit systemic IgG antibodies