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

• properties as a fluorogenic noncovalent DNA or RNA binder, many representatives of this class of dyes have been developed [3][4][5][6][7]. Thiazole orange does not fluoresce in the free state in solution. Fluorescence appears when the rotation about the monomethine bridge between the two heterocyclic

• ]. 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

• with its 5′-cap is of central importance for the cell. Many studies involving mRNA require reliable preparation and modification of 5′-capped RNAs. Depending on the length of the desired capped RNA, chemical or enzymatic preparation – or a combination of both – can be advantageous. We review state-of

• ; enzymatic capping; methyltransferase; RNA; Introduction The 5′-cap is a hallmark of eukaryotic mRNA and involved in numerous interactions required for cellular functions. Chemically, the 5′-cap consists of an inverted 7-methylguanosine connected to the rest of the eukaryotic mRNA via a 5′–5′ triphosphate

• binding complex (CBC) [9][10] in the nucleus required for nuclear export and the eukaryotic translation initiation factor 4E (eIF4E) [11] in the cytoplasm which is indispensable for cap-dependent translation. Additionally, capped RNA serves as a marker for the innate immune system to distinguish

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

• , different forms may be detected, i.e., the circular, linear and supercoiled topoisomers (Figure 8; in some preparations of pDNA, even after RNAse treatment, RNA can be present). Two sets of experiments were carried out: the first one (Figure 8a) with the same N/P ratios for each AmCD, and the second one

• the linear one at 38.5. Both, CD2 and CD3 bound the supercoiled conformation of pDNA almost completely at N/P 49.5, the linear one at 38.5 and 27.5, respectively. The lack of RNA migration occurred at N/P 16.5, 27.5 and 16.5 for CD1, CD2 and CD3, respectively. The minimum N/P ratios for complete

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• measurements can be used to study ligand–protein [12] and protein–protein interactions [13]; membrane proteins [14][15][16] and membrane-associated peptides [17][18]; equilibria among conformations of RNA [19], DNA [20], and peptide nucleic acids (PNA) [21]; and many others. Particularly recent is the

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• ]. The group of Ravoo also conjugated arylazopyrazoles to amphiphilic cyclodextrin derivatives that form vesicles triggered by light [17]. A star-shaped polycationic CD derivative with many breakable, intrinsic, disulfide linkages forms nanoparticles with messenger RNA and drugs and is particularly

β-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling aqueous networks designed for controlled complexation and release of small molecules

• Liang Yan,
• Duc-Truc Pham,
• Philip Clements,
• Stephen F. Lincoln,
• Jie Wang,
• Xuhong Guo and
• Christopher J. Easton

Beilstein J. Org. Chem. 2017, 13, 1879–1892, doi:10.3762/bjoc.13.183

• , fluconazole [40] and curcumin [37], along with larger species exemplified by RNA and DNA segments [26][32][33][36][39][47]. Some systems are designed to target specific tissues [26][35]. We are particularly interested in the extent to which small molecule guest complexation and release characteristics may be

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

• ) histopathological examination [64]. Alternatively, serological testing has been proposed and promising results were obtained in a case control study in Ghana [65]. More recently, the detection of mycolactone from patient biopsy samples via LC–MS [66] and RNA aptamer binding [67] has been suggested, but the

• nor did the silencing of (N)-WASP by RNA interference alter the suppression of secretory and membrane protein production by mycolactone. The angiotensin pathway was identified as a third target of mycolactones by Brodin and co-workers in 2014 [104]. It has been known for some time that mycolactone is

• course of mycolactone-mediated apoptosis. Silencing Bim and Fas by RNA interference proved that Bim is the key driver of mycolactone-mediated apoptosis while Fas upregulation may represent a passive bystander effect. Based on these results and considering the remote similarity of mycolactones with

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

• ], and RNA-worlds [7], or designated by a general concept such as the metabolism- and gene-first scenarios [8]. This multi-faceted approach (Figure 2), whilst suffering somewhat from a lack of effective integration or cohesion, has nonetheless permitted the accumulation of essential insights in the

• characteristics of various biomolecules, e.g., the catalytic activity of RNAs and their evolution potential [9][10][11], as well as processes that were essential for their syntheses, such as Fischer–Tropsch-like reactions [12], non-enzymatic RNA [13] or peptide polymerization [14]. Moreover, it has also allowed

• life to emerge [29], distinct geochemical environments could have not only produced specific chemicals, but could also have contributed to their evolution at different stages. For instance, the idea of RNA polymers as information components, precursors of a genetic system, can be partially realized

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

• will defend the view that in order to reconstruct this process a strict ‘bottom-up’ approach should be pursued, starting with chemical precursors of biomolecules, rather than with fully functional biomolecules. Whereas the encapsulation of biopolymers (DNA, RNA, proteins) or cell extracts in self

• macromolecular structures, like proteins or nucleic acids, took control of metabolic dynamics. In fact, although the mainstream way to experimentally investigate protocells and their evolutionary capacity has been to take a ‘semi-synthetic’ approach (encapsulating populations of RNA or DNA polymers inside lipid

• 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

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• . Several of protocols developed for the soluble-supported synthesis allow the preparation of both DNA and RNA oligomers of limited length in gram scale without any special equipment, being evidently of interest for research groups that need oligonucleotides in large amounts for research purposes. However

• , none of them has really tested at such a scale that the feasibility of their industrial use could be critically judged. Keywords: DNA; oligonucleotides; RNA; soluble support; synthesis; Introduction The synthesis of oligonucleotides (ONs) consists of linking nucleosides to each other in a specified

• used to assemble a 21-mer RNA sequence in gram scale [61] (Scheme 9). First, the DMTr group was removed with DCA in DCM and the detritylated support was precipitated from MeOH. A base-moiety-protected (APac, GiPac, CAc) 5´-O-DMTr-2´-O-TBDMS-nucleoside 3´-(2-cyanoethyl-N,N-diisopropylphosphoramidite

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• described by Darwin in his famous work On the Origin of Species, but are still not understood in full detail [2]. It was only in the 1960’s that Spiegelman extended the scope of Darwinian evolution to chemical systems by studying the evolution of RNA-complexes [3]. In these experiments RNA was replicated

• using enzymes “borrowed” from contemporary biology. The outcome of the selection experiments was the shortening of the RNA sequence, as shorter sequences could be replicated faster. It was soon realized that a better understanding about how evolution acts on the molecular level would not only provide

• recently reported in an in vitro evolution experiment with replicating RNA species [11]. There is of course a constraint on the number of mutations that can occur without losing too much hereditary information from the parent molecules. In the same work, Eigen showed that unless mutation rates were

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

• summary, the most likely compounds that make the very first metabolic pathways are charged compounds with one to three carbon atoms, amino acids and a variety of peptides or related compounds, certainly not RNA [25]. Phosphates, with their remarkable metastable state in water were selected as surface

• nucleotides (and even more RNA) at the origin of life should be able to account for a steady synthesis of this molecule. In passing, this also argues fairly strongly against an origin involving hot temperatures, because heat considerably increases ribose instability [32]. Another argument for a late

• requirement would be that some catalysis allowed for a redox reaction (this is a general requirement of cell metabolism, involved in many metabolic steps, that is difficult, if not impossible, to fulfil using only RNA). As a consequence, primitive metabolic pathways would subsequently synthesise general

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• rings and have shown important biological properties [5][6][7][8][9][10][11][12]. For example, macrocyclic aminoglycoside analogues have shown binding with the trans-activating region (TAR) RNA of the human immunodeficiency virus (HIV); an attractive target for RNA-based drug discovery [13]. Further

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• diameter range can be obtained [4]. Moreover, this synthetic procedure allows to introduce different types of carbohydrates and other ligands (i.e., polyethylene chains, lipids, peptides, DNA, RNA or fluorescent dyes) in controlled ratios [4]. A modification of this technique consists in the application of

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• ; Introduction Endogenous nucleosides are involved in DNA and RNA synthesis, cell signalling, enzyme regulation and metabolism etc. [1][2]. Therefore, the synthesis of novel nucleosides to mimic their physiological counterparts has potential therapeutic significance, which has led to the development of a large

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

• developments [13][14] have supported a kinetically based view. Taking that kinetic approach, the concept of natural selection was able to be extended beyond biology so as to be applicable at the molecular level. Both views progressed separately in a context dominated by the RNA world hypothesis, though that

Conjecture and hypothesis: The importance of reality checks

• David Deamer

Beilstein J. Org. Chem. 2017, 13, 620–624, doi:10.3762/bjoc.13.60

• polymerization is obvious and was first proposed years ago [19]. Lahav and White [20] adopted the approach and demonstrated that peptide bonds could be produced using clay as a catalyst. The approach was largely abandoned with the advent of the RNA World scenario that suggested a way for life to begin in

Adsorption of RNA on mineral surfaces and mineral precipitates

• Elisa Biondi,
• Yoshihiro Furukawa,
• Jun Kawai and
• Steven A. Benner

Beilstein J. Org. Chem. 2017, 13, 393–404, doi:10.3762/bjoc.13.42

• /bjoc.13.42 Abstract The prebiotic significance of laboratory experiments that study the interactions between oligomeric RNA and mineral species is difficult to know. Natural exemplars of specific minerals can differ widely depending on their provenance. While laboratory-generated samples of synthetic

• minerals can have controlled compositions, they are often viewed as "unnatural". Here, we show how trends in the interaction of RNA with natural mineral specimens, synthetic mineral specimens, and co-precipitated pairs of synthetic minerals, can make a persuasive case that the observed interactions reflect

• the composition of the minerals themselves, rather than their being simply examples of large molecules associating nonspecifically with large surfaces. Using this approach, we have discovered Periodic Table trends in the binding of oligomeric RNA to alkaline earth carbonate minerals and alkaline earth

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

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

• were harvested and total RNA was extracted. The differential regulation of PPL_09347 was determined by RT-qPCR. Synthetic glorin (1) and glorinamide 2 led to similar expression of PPL_09347, comparable to commercial glorin as positive control (Figure 2). While a small baseline induction of PPL_09347

• ), synthetic glorin (1), or glorinamide 2 (100 µM stock solutions with 3% DMSO) or water were added to the cells every 30 min for 1 h. Cells were centrifuged for 30 min after the last addition and stored in pellets of 2 × 107 cells at −80 °C. Total RNA was prepared using the QIAGEN RNeasy kit and cDNA was

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

• first report [21]. The orientation of the 2’-OH group in the arabino configuration towards the major groove yields hybrids with RNA that show a slightly lower thermal stability compared to DNA/RNA hybrids. In order to evaluate this structural influence for our fluorescently labelled oligonucleotides, we

• the dyes into the major groove led them find a better orientation than in the minor groove, with respect to the DNA helix with enhanced fluorescence intensities. The dyes D1–D4 as energy donors were combined with dyes D5–D9 as energy acceptors (Scheme 3). This approach follows our concept of “DNA/RNA

• λexc = 488 nm (argon ion laser), λem = 490–550 nm (green) and 675–800 nm (red), scale bar = 20 µm. 2’-Propargylated nucleosides as “clickable” DNA/RNA building blocks with ribo (1) and arabino (2) configuration. Synthesis of phosphoramidite 7 and modified DNA. a) TIPDSiCl2, pyridine, 2 h at 0 °C, 16 h

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• Databank (PDB), which was first introduced in 1970s, is a global resource that contains a wealth of 3D information about experimentally determined biological macromolecules [82][83]. The structures in the PDB are individual macromolecules, protein–DNA/RNA or protein–ligand complexes. Experimental methods

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

• genetic molecule RNA (see below) and is also an important component of coenzymes (ATP, FAD and NAD). In 1992, Aoyama et al. reported on the selective complexation of pentoses and hexoses by β-CD [95]. Based on competitive inhibition of the 8-anilinonaphthalene-1-sulfonate binding followed by fluorescence

• phosphodiester bonds. There are two types of nucleic acids according to the sugar: deoxyribose and ribose for deoxyribonucleic acid, DNA, and ribonucleic acid, RNA. Nucleic acids function in encoding, transmitting and expressing genetic information. As nucleic acids allow the synthesis of proteins their

• 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

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• Elisabeth Mairhofer Elisabeth Fuchs Ronald Micura Institute of Organic Chemistry and Center for Molecular Biosciences, University of Innsbruck, Austria 10.3762/bjoc.12.250 Abstract Access to 3-deazaadenosine (c3A) building blocks for RNA solid-phase synthesis represents a severe bottleneck in

• modern RNA research, in particular for atomic mutagenesis experiments to explore mechanistic aspects of ribozyme catalysis. Here, we report the 5-step synthesis of a c3A phosphoramidite from cost-affordable starting materials. The key reaction is a silyl-Hilbert–Johnson nucleosidation using unprotected 6

• building blocks for RNA solid-phase synthesis represents a severe bottleneck in modern RNA research, in particular for studies that aim at the mechanistic elucidation of site-specific backbone cleavage of recently discovered ribozyme classes, known as twister, twister sister, pistol, and hatchet RNA