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

Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent

• Kohei Koyanagi,
• Yoshinori Takashima,
• Takashi Nakamura,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2016, 12, 2495–2502, doi:10.3762/bjoc.12.244

• catalyst; Introduction The folding of proteins in biological systems, the replication of DNA, and specific substrate recognition by enzymes play important roles in forming supramolecular structures, achieving functions, and maintaining life [1][2][3][4][5][6]. The crystal structures of RNA polymerase, DNA

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• RNA and DNA, respectively. The mechanisms of molecular recognition and cell interaction are mostly explained by the interaction of carbohydrates with proteins, called lectins, exposed at the cell surface. This process, on the one hand, allows bacteria to interact with other cells during infection, but

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

• negligible. Interaction between MGB-TFO conjugates and the target duplex Our previous studies with parallel TFO-polyamide conjugates demonstrated that conjugated polyamides poorly stabilized both DNA and 2'-O-methyl-RNA parallel triplexes, and there were independent interactions between polyamide or TFO

• ) catalysis is absolutely necessary for a successful Huisgen 1,3-cycloaddition reaction. Physicochemical studies of the interaction between the obtained conjugates and target dsDNA confirmed our previous results with the conjugates of DNA and 2'-O-methyl-RNA that one molecule of the polyamide attached to

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• humans, where they function by inhibiting RNA polymerase II [111]. In the α-amanitin pathway [112], a prolyl oligopeptidase-like enzyme catalyses both hydrolysis of the leader peptide and transpeptidation to yield a backbone macrolactam [113]. No distinguishing features have been identified to indicate

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• currently being used for the treatment of growth hormone deficiency as a potent and orally active GHSR agonist [10]. YK-4-279 can potently inhibit the growth of Ewing’s sarcoma by blocking the interaction between the oncogenic protein EWS-FLI1 and RNA helicase A (RHA) [11]. Interestingly, only (S)-YK-4-279

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• methicillin-resistant Staphylococcus aureus (MRSA) [18][19] and vancomycin-resistant Enterococcus (VRE) [20]. This development raises the demand for antibiotics exploiting yet unused modes of action. Potential targets within bacteria include peptidoglycan biosynthesis, protein biosynthesis, DNA and RNA

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• crucial step in the origin of life was the prebiotic formation of information carrying polymers. For the polymers playing this role in contemporary biochemistry, i.e., DNA and RNA, such a process appears difficult owing to the low reactivity and solubility of phosphate. Indeed, all of the enzyme-free

• were then subjected to digestion by P1 nuclease (Figure 4C). Thymidine and thymidine-5´-monophosphate accounted for approximately 78% of the final product mixture. As cleavage by P1 nuclease is limited to 3´,5´-phosphodiester linkages of single-stranded DNA or RNA, the results of the digestion

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• prokaryotic RNA polymerase (RNAP) as mode of action for myxopyronins and corallopyronins [95][97]. Later on, mutagenesis experiments as well as binding studies indicated that the antibiotics interact with the RNAP switch region [104][105], which acts as a hinge mediating conformational changes during

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• still hampered today. Difficulties arise because of several issues: Due to the highly charged character of RNA molecules, the electrostatic contributions are quite large. Small, pair-wise errors might sum up to an erratic description of the total energy [24]. Second, the relevant RNA/drug complexes show

• a pronounced flexibility. It might therefore be misleading to focus on the solid state structures of available nucleotide/guest complexes alone [25]. A third obstacle is the intrinsic deficiency of empirical force fields especially for DNA/RNA structures (“force-field polymorphism”). A thorough

• force field method evaluation is therefore a prerequisite for any meaningful in silico study, especially of processes that involve molecular recognition by DNA/RNA hosts [26]. Though there are many success stories in the literature, it is not all it's cracked up to be in the euphoric 1990s, when

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• atmosphere of his group inspires all members to go as far as possible in academia. Early academia The question everyone has to confront when starting in academia is “what to do?”. Initially I took an easy route. My post-doctoral work with Ronald Breslow was focused on enzyme mimics for the hydrolysis of RNA

• for sensing purposes. The impetus for doing so was driven by an attempt to have a higher impact with our work, but, admittedly, was also due to serendipity. Several events moved our group’s research toward sensing applications. One was having a synthesis to create 9 as an RNA hydrolysis catalyst

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• , in vivo infection studies coupled with methods such as RNA sequencing, can lead to further insights into the role and expression levels of potentially new secondary metabolites. Conclusion Insects provide experimentally tractable and cost-effective model systems to investigate the evolutionary

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

• ; intercalation; macrocycles; multi-target drug discovery; RNA recognition; RNase mimic; Review Early childhood and overview I was born on October 8, 1957 in Evanston, Illinois, the second of three boys. Our parents, Howard E. Zimmerman and Jane Zimmerman, née Kirschenheiter, were very much in love and also

• small molecules to treat DM2, which originates in a CCUG expansion, but Lien Nguyen, Chun-Ho Wong, and JuYeon Lee used similar rational design approaches and found lead agents that are selective for this RNA as well [89]. Although the gain of function mechanism that has CUGexp sequestering MBNL1 is well

• CUGexp, also binding CUGexp that slips through inhibiting its sequestration of MBNL1, and, with the catalytic amino/ammonium/imidazole groups, slowly cleaving the CUG-RNA to prevent RAN translation [92]. Edwin Chan and his group again studied the in vivo activity of our compounds, showing that 32

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• associative forces including hydrogen bonding, coordinate bonding, electrostatic interactions and hydrophobic interactions is ubiquitous in nature. This is exemplified by the use of DNA and RNA complementarity [1][2] and polypeptide helix formation [3][4] to produce three-dimensional structures and materials

A convergent, umpoled synthesis of 2-(1-amidoalkyl)pyridines

• Tarn C. Johnson and
• Stephen P. Marsden

Beilstein J. Org. Chem. 2016, 12, 1–4, doi:10.3762/bjoc.12.1

• as the antitumour antibiotic kedarcidin chromophore 1 [2] and the RNA polymerase inhibitor cyclothiazomycin B1 2 [3] (Figure 1). Additionally, the motif is commonly incorporated into synthetic pharmaceutical candidates, for example in the factor XIa inhibitor 3 [4], the orally-active renin inhibitor

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

• highlight some of these stories of unexpected results and what we learned from them. During my initial brainstorming of project ideas, I was very drawn to the idea of working with DNA split aptamers. These recognition elements are comprised of two DNA (or RNA) sequences that selectively assemble in the

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• -lines [14][15][16]. Moreover, some 6-heterocyclic substituted purine ribonucleosides also demonstrate strong antiviral activities [17]. Purine derivatives such as, 2’-β-C-methyl-6-substituted purine nucleosides exhibit promising anti-HCV activity by blocking RNA dependent RNA polymerase [18][19][20

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• -ribosomal peptides Non-ribosomal peptides often exhibit a high bioactivity and are biosynthesized by non-ribosomal peptide synthethases (NRPS) [33], which work RNA-independent and catalyze the assembly of both proteinogenic and non-proteinogenic amino acids in a modular fashion. Moreover, NRPSs can contain

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• products have been shown to be potent antibiotics targeting the newly identified switch region of the bacterial RNA polymerase [24]. Furthermore the promiscuity of MxnB regarding its substrate specificity has been used in mutasynthesis experiments to produce novel myxopyronin derivatives [25]. Recently the