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

Pd(OAc)₂-catalyzed dehydrogenative C–H activation: An expedient synthesis of uracil-annulated β-carbolinones

• Biplab Mondal,
• Somjit Hazra,
• Tarun K. Panda and
• Brindaban Roy

Beilstein J. Org. Chem. 2015, 11, 1360–1366, doi:10.3762/bjoc.11.146

• control agents for receptor research on bioenzyme inhibitors, such as the inhibition of HLE (human leukocyte elastase) [15][16][17][18]. Uracil, on the other hand, is one of the four nucleobases of RNA. It holds immense importance from a pharmaceutical and biological point of view [19]. For example, 5

Is organic chemistry science – and does this question make any sense at all?

• Andreas Kirschning and
• Thomas A. C. Reydon

Beilstein J. Org. Chem. 2015, 11, 893–896, doi:10.3762/bjoc.11.100

• conditions (molecular recognition, self-assembly and dynamic combinatorial chemistry) and how their molecular composition would be; the question why nature developed DNA and RNA that utilize ribose and 2-deoxyribose as central nucleotide building blocks instead of the more abundant and readily available

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• adaptive, divalent receptor as a protein target. As a model protein the tandem-WW-domain of the pre-mRNA splicing factor formin binding protein 21 (FBP21) was selected [13][14][15]. Considering the importance of FBP21 in the activation of RNA splicing, successful ligands should be valuable tools to

• architecture connected with a flexible linker the tandem WW-domains of the protein FBP21 were selected. FBP21 is a protein component of the spliceosome, the multiprotein complex in the nucleus of cells responsible for the processing of primary RNA-transcripts. The two WW domains of FBP21 bind to proline-rich

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

• ; Introduction Since the discovery of RNA interference (RNAi) and awareness of its role in posttranscriptional gene silencing, tremendous efforts and capital have been devoted to the development of therapeutics based on this pathway [1]. So far, there are at least 22 RNAi-based drugs in clinical trials and many

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

• and Nutrition, Novum, SE-141 83 Huddinge, Sweden 10.3762/bjoc.11.55 Abstract Tris(2-aminobenzimidazole) conjugates with antisense oligonucleotides are effective site-specific RNA cleavers. Their mechanism of action is independent of metal ions. Here we investigate conjugates with peptide nucleic

• acids (PNA). RNA degradation occurs with similar rates and substrate specificities as in experiments with DNA conjugates we performed earlier. Although aggregation phenomena are observed in some cases, proper substrate recognition is not compromised. While our previous synthesis of 2-aminobenzimidazoles

• the one hand, they can improve our mechanistic understanding of natural ribonucleases and of phosphodiester reactivity in general. On the other hand, a wide range of practical applications is conceivable for such RNA cleavers ranging from tools in molecular biology to chemotherapeutics targeting mRNAs