In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• tetra-ortho-fluoroazobenzene–PNA conjugates have promising properties (fast reversible isomerization, exceptional thermal stability, high isomer conversions and sensitivity to visible-light irradiation) as reversible modulators to control oligonucleotide hybridization in biological contexts. Furthermore

• , we verified that this switchable modification delivers a slightly different hybridization behavior in the PNA. Thus, both melting experiments and strand-displacement assays showed that in all the cases the trans-isomer is the one with superior binding affinities. Alternative versions, inspired by our

• hybridization has demonstrated an enormous potential to regulate on-demand biological responses such as gene expression [1]. There are indeed a number of successful examples based on photocaged strategies [2][3][4][5], in which modified nucleic acids interfere irreversibly with gene expression in vitro [6][7

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• prospect of the tetrazole hybridization strategy in drug discovery. Among the most versatile methods for obtaining tetrazoles are the Ugi-azide four-component reaction (Ugi-azide-4CR) [14][15][16] and the 1,3-dipolar cycloaddition of azides with (acyl)cyanides [17][18]. The Ugi-azide-4CR enables the

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• generate a vast number of (poly)cyclic hydrocarbon scaffolds. Remarkably, this complex chemical reaction, comprising changes in bonding, hybridization as well as the introduction of specific stereochemistry, is performed in a single reaction cascade without consumption of a cofactor [11]. In this review we

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• analysis of the bond lengths has shown that the formally single exocyclic C1–N3 bond is shorter than the double endocyclic C6–C1 bond (1.336(6) Å and 1.354(9) Å, respectively).The C1 and C6 atoms are planar indicating their sp2 hybridization. Such a distribution of electron density allows to discuss the

• indicating their sp2 hybridization. Such a distribution of electron density allows discussing the zwitter-ionic form and considering the structure of 19a as superposition of two resonance structures similar to 16a (Scheme 6). Conclusion In the described three-component reactions with aldehydes or isatins and

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• of higher complexity by employing simpler, more efficient, catalytic methods that are also environmentally friendly. Molecular hybridization has emerged as an interesting strategy for the synthesis of bioactive molecules with improved properties by combining two or more pharmacophore fragments in a

Adhesion, forces and the stability of interfaces

• Robin Guttmann,
• Johannes Hoja,
• Christoph Lechner,
• Reinhard J. Maurer and
• Alexander F. Sax

Beilstein J. Org. Chem. 2019, 15, 106–129, doi:10.3762/bjoc.15.12

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

• 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

• aminoalkyl phosphoramidate-linked oligonucleotide 18. To study the hybridization properties of such cationic oligonucleotide analogues with native DNA and RNA, Letsinger and co-workers performed UV-monitored thermal denaturation experiments [40][41]. In the case of the modified deoxyadenosyl dimer 11

• , hybridization with native RNA-TPoly as well as with DNA-TPoly strands was evident and the complex formed more stable than comparable complexes involving the native d(ApA) DNA reference. An increase of the measured Tm of ≈10 °C for complexes of the aminoethyl phosphoramidate-linked dinucleoside 11 with RNA and

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• homopolymer templates, Joyce and Orgel concluded that the structure and hybridization status of templates was important for high-yielding copying reactions [26]. In a later series of papers with specific, synthetic sequences, Wu and Orgel reported that primer extension proceeds poorly if too many weakly

• complexes between free nucleotides and primer–template duplexes. This required methodology adjusted to measuring weak binding, i.e., much weaker than the strand-to-strand hybridization of oligonucleotides leading to duplexes, which is usually monitored by UV-melting analysis [43]. We chose NMR spectroscopy

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

• a hypoxia-labile modification either in the phosphate backbone to mask the negative charge and provide better tumor selectivity [25][26] or at the nucleobase to modulate the hybridization properties with the target [27]. In all cases, a nitro-derivative-modified thymidine phosphoramidite was

• , demonstrating the importance of hybridization in the RNAi mechanism. Deiters et al. also applied the NPOM photosensitive group for gene silencing using antisense oligodeoxynucleotides (ODNs) in mouse fibroblast 3T3 cells transfected with the Renilla luciferase plasmid [84]. Three and four modifications

• partitioned along the sequence of the antisense ODN prevented hybridization to RNA targets and consequently inhibited the antisense activity blocking RNase H catalyzed degradation of mRNA. Upon irradiation at 365 nm, the NPOM groups were completely removed and the antisense activity was restored to the level

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• with the azasiline donor, OLEDs displaying the unprecedented EQE of 22.3% were obtained [46]. As specificity, azasiline is a 6-membered heterocycle comprising a silicon atom introduced instead of a carbon atom to enlarge the HOMO–LUMO gap and lower the HOMO level. Due to the sp3 hybridization of the

Fluorogenic PNA probes

• Tirayut Vilaivan

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

• unbound probes, which is most commonly achieved by solid phase hybridization followed by washing to eliminate the unbound probes before performing the fluorescence readout. These assays require multiple steps, and so are time-consuming making them unsuitable for real-time monitoring, such as nucleic acid

• developments in the areas of fluorogenic PNA probes. Some examples of PNA probes for nucleic acid hybridization and detection that may not be strictly fluorogenic by definition have been included where deemed suitable. Overview of PNA and fluorescent PNA probes Peptide nucleic acids (PNA) are a unique class of

• have successfully employed PNA probes include array hybridization [36][37] and staining of intracellular nucleic acids by fluorescence in situ hybridization (FISH) [38][39]. For the same reasons explained above in the case of oligonucleotide probes, it is more desirable to develop a fluorogenic PNA

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

• ., pointing towards the nitro group) [14]. As was mentioned in the synthesis part above, recently we also have developed tCO as an internal fluorophore for RNA systems [50]. The incorporation into RNA oligonucleotides and hybridization with a complementary strand results in normal A-form RNA duplexes

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

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• -initiation of MLA in Scheme 2. We propose that a homolytically H–C cleavage takes place in a first step yielding two radicals. This process is accompanied by a change of hybridization from a tetrahedral sp3 structure of the chiral center to a trigonal planar sp2 structure of the resulting radical. Scheme 2

• . The above mentioned hybridization change as driving force for C–H cleavage is verified in the reduced bond length of the C–CH3 bond from 1.542 Å (MLA) to 1.479 Å for the corresponding radical. This clearly indicates a stabilization of this C–C bond after C–H cleavage (Figure 3). Since only soluble

Experimental and theoretical investigations on the high-electron donor character of pyrido-annelated N-heterocyclic carbenes

• Michael Nonnenmacher,
• Dominik M. Buck and
• Doris Kunz

Beilstein J. Org. Chem. 2016, 12, 1884–1896, doi:10.3762/bjoc.12.178

• pyrido-annelated N-heterocyclic carbenes, an NHC class that was introduced by Weiss and co-workers (Figure 1) [39][47]. They pointed out the unusual high s-character of that carbene σ-orbital by a 1JCH coupling constant of 232.6 Hz, which corresponds to a hybridization of only sp1.15. Although they had

The role of alkyl substituents in deazaadenine-based diarylethene photoswitches

• Christopher Sarter,
• Michael Heimes and
• Andres Jäschke

Beilstein J. Org. Chem. 2016, 12, 1103–1110, doi:10.3762/bjoc.12.106

• hybridization upon switching [43][44]. This new class of diarylethenes showed promising photophysical and photochemical properties, such as the location of the photostationary states, reversibility of switching, thermal stability, and fatigue resistance. In 2013 we developed a 2nd generation of diarylethene

Direct estimate of the internal π-donation to the carbene centre within N-heterocyclic carbenes and related molecules

• Diego M. Andrada,
• Nicole Holzmann,
• Thomas Hamadi and
• Gernot Frenking

Beilstein J. Org. Chem. 2015, 11, 2727–2736, doi:10.3762/bjoc.11.294

• ones. The X–Ccarb–X (X = N, C, O and S) angle in the five-membered rings slightly varies between 99.6° (10) and 105.6° (15) and is slightly larger (120.1°) in the acyclic carbene 5. This angle is often associated with the σ-donor properties which are related to the spx hybridization of the carbene lone

• carbon in Figure 3b indicates the polarization (change in hybridization) which takes place during the bond formation. The charge flow which is associated with the π-donation X(π)→Ccarb shows the expected direction from nitrogen to carbon. The charge flow which is associated with the three dominant

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• . According to this logic, split aptamers will function best when the enthalpy for hybridization between the DNA strands is tuned such that in the absence of the ligand, this enthalpic gain is not quite sufficient to overcome the entropic cost of assembly. This poises the DNA strands at the brink of assembly

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• oligomeric interactions involving multiple carbohydrate units. In efforts to recapitulate the diverse spatial arrangements of the carbohydrate units, assemblies based on hybridization of nucleic acid conjugates have been used to display simplified ligands with tailored interligand distances and valences. The

• the geometry of the oligomeric interactions provided an important precedent [10] and has stimulated intense research in glycomimetics, glycodendrimers, and glycopolymers [11][12]. Over the past decade, there has been a growing interest in using oligonucleotide hybridization [13][14][15] to scaffold

• the assembly of glycans in order to tailor spatial geometry [16]. Attractive features of this hybridization-based supramolecular scaffold are that double strand nucleic acid is fairly rigid with well-defined nucleotide spacing and that the valence and ligand combination can be adjusted through the

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• the signals relative to the substrate peak suggests that cleavage occurred only in the non-hybridized part of the RNA. We explain this effect by incomplete PNA–RNA strand separation during electrophoresis due to stronger hybridization resulting from the G/C-rich sequence of the conjugate (10 G/C-base

• -conjugate 13, no signal shift is seen with the 10mer-conjugate 11. However, the cleavage occurs in a nonspecific way in nearly all positions not protected by hybridization with PNA (lane c). Though site specificity is low in this case, conjugate 13 is nevertheless substrate specific and does not degrade

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• molecular recognition as well. The most important natural example of sequence specific, multivalent molecular recognition is the hybridization of complementary DNA strands via the base pairing of adenosine and thymine respectively guanine and cytosine. Within the last years these binding motifs have been

• artificial amino acids no significant selectivity was observed [40]. In this work we present an alternative approach to realize the hybridization of complementary strands mediated by multivalent host–guest interaction. We used α- and β-CD because of their well-known and regiospecific modifiability for the

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• -pairing geometry. The added information density allows larger numbers of synthetic fragments to self-assemble without off-target hybridization, hairpin formation, and non-canonical folding interactions. The AEGIS pairs are then converted into standard pairs to produce a fully natural L-DNA product. Here

• possible interaction, the presence of “strong” and “weak” G:C and A:T pairs makes design challenging. Also complicating self-assembly of single-stranded DNA fragments are folded single-strand structures (such as hairpins) that compete with desired inter-strand hybridization. A rich repertoire of non-Watson

• -bonding units displayed by the nucleobases, allowing them to pair orthogonally within the geometry of the Watson–Crick pair (Figure 2). With higher information density in AEGIS, more fragments should self-assemble with fewer off-target hybridization, fewer hairpins, and fewer close mismatches that slow

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• + SG. In a second series of experiments we used an unlabelled target DNA (6) for duplex formation at the lipid bilayer and added only a DMSO solution of Sybr Green I to the cis compartment of the bilayer slide. As can be seen from Figure 7 also the hybridization of an unlabelled target oligomer 6 with

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

• strand will need to be filled in with orthogonal 5' to 3' chemistry. A dT nucleoside analog with an exocyclic aziridine moiety has been chemically incorporated into poly-T ODN. Upon hybridization with a complementary poly-A strand, the aziridine group is attacked by the exocyclic amino group of the

• nucleobases in which an exocyclic functionality has been substituted by a vinyl group. Upon hybridization with a complimentary, unmodified strand, the vinyl group is attacked by the nucleophilic exo- or endocyclic nitrogen of the partnering base, forming a cross-linked base pair [32][33][34]. While the cross

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• . The C9–C10–C11 bond angle of 108–110° indicates that C10 can accommodate both planes and does not distort from the normal sp3 hybridization. A schematic rendition of the macrocycle that depicts the planar units and their orientations is also included in Table 1. The three rigidifying units create a