Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• nucleic acids, where we showed that cationic nanoparticles could bind to anionic DNA and inhibit transcription [37]. We also developed a number of strategies for delivery of small molecules, including glutathione-mediated release of covalently attached thiols [38], as the effective release of drugs

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

• ][13][14][15]. Recently a new class of TFOs containing covalently linked intercalating pyrene moieties, so-called "twisted intercalating nucleic acids" (TINA), has been described [16][17]. TINA-TFOs form stable and specific triplexes with target dsDNA at physiological conditions. It has been shown that

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

• in which a purine nucleobase represented one of the aryl rings of the photoswitch (Figure 1B). Importantly and different from most other approaches towards photoswitchable nucleic acids, the nucleobase constituted an active part of the photoswitch (rather than an appendage), changing its bonding and

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

• of nucleic acids. 31P NMR spectrum (162 MHz, D2O) of the crude product mixture after refluxing equimolar amounts of thymidine and triethylammonium phosphite and 4 equiv of S8 in toluene for 90 h. IE HPLC trace of the crude product mixture after refluxing equimolar amounts of thymidine and

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

• self-assembly; nucleic acids; Introduction “Jennifer is not skilled at science.” This judgment was delivered upon me at the age of fourteen by my eighth grade science teacher, and was part of a recommendation that I not be placed on the science-intensive track of study as I entered high school. The

• my Ph.D. studies, I had tremendous fun designing and studying organic foldamers, but I also began to be attracted to the especially privileged molecular recognition and self-assembly properties of nucleic acids. I think that Jeff actually recognized this before I did, as he chose the additional

• into who I was as a scientist, at least at that moment in my career. All of the project ideas that made the final cut involved using a combination of molecular recognition, self-assembly, and nucleic acids to build functional architectures for applications in biosensing or bioimaging (Figure 1). As my

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• supramolecular community should build much larger synthetic hosts. How can this be done? One approach is to create covalently linked polymers that are programmed to fold up into three dimensional structures that mimic the topologies of proteins and nucleic acids. Perhaps a more facile fabrication strategy is to

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• conditions used to prepare compound 2. This step aimed to have an alkylating probe that might target nucleic acids or proteins in the tested biological systems. The 1,2,3-triazole-bridged bicholesterol 13 (Scheme 3) was prepared in excellent yield. The H-5 signal of triazole (1H NMR) also was observed as

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• that govern the interaction of nucleic acids with small molecular entities and other biopolymers has increased. In particular, for NMR spectroscopic studies of such interactions, oligonucleotides are often required in quantities that are inconvenient to prepare by laboratory scale solid-phase synthesis

• -protected oligodeoxyribonucleotide trimer 3’-pTpdCBzpdGibu-5’ as its 3’-(2-chlorophenyl phosphate) was achieved by reductive cleavage of the disulfide bond. Keywords: disulfide linker; oligodeoxyribonucleotides; phosphotriester chemistry; precipitation; soluble support; Introduction Synthetic nucleic

• acids have been used to regulate gene expression through different mechanisms of action, such as antisense oligonucleotides [1][2], ribozymes [3], interfering RNAs (siRNA) [4][5] and immunostimulatory CpG [6] based therapeutics. At the same time, the interest in detailed understanding of the factors

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• they constitute three key types of biomacromolecules–proteins, nucleic acids, and carbohydrates. Inspired by this molecular foundation resulted from evolution, we are developing biomaterials that consist of the covalent conjugates of these three classes of the basic building blocks of life. For example

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• lipo-oligonucleotides. Keywords: lipid bilayer; lipo-oligonucleotides; nucleic acids; nucleolipids; Introduction For proper cell function, the biosynthetic lipophilization of proteins and carbohydrates, such as palmitoylation and farnesylation, is of decisive importance [1]. The same seems to be true

• formation at a lipid bilayer–water phase boundary using SYBR Green I staining. For this purpose, various nucleic acids of different length and sequence were lipophilized by appending a terminal non-nucleosidic lipid head group and then bound on the surface of an artificial lipid bilayer. Subsequently

• lipophilization and studies on the interactions of lipophilized nucleic acids with lipid bilayers is of growing importance. As lipophilic head groups we used a series of nucleolipid cyanoethyl phosphoramidites that were recently synthesized [13][14][15][16][17]. Results and Discussion Figure 1 indicates the

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

• single strand stretches that remain flexible. Such assemblies can also be generated in spatially addressable format using DNA microarrays. At the core of this technology is the ability to conjugate biologically relevant glycans or glycomimetics to nucleic acids. Herein, we present an update of 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

• required an HgO induced cyclization step, a mercury free variant is described herein. Keywords: antisense; fluorescence correlation spectroscopy; guanidine; miRNA 20a; peptide nucleic acids; Introduction Sequence specific artificial ribonucleases are an attractive research target for several reasons. On

• of RNA cleavers to oligonucleotide analogues such as peptide nucleic acids (PNA) [4]. The benefits of oligonucleotide analogues are higher affinity towards RNA [5] as well as improved resistance against biodegradation [6]. Furthermore, PNA can be applied to block miRNA functions in cell culture

• 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

A procedure for the preparation and isolation of nucleoside-5’-diphosphates

• Heidi J. Korhonen,
• Hannah L. Bolt and
• David R. W. Hodgson

Beilstein J. Org. Chem. 2015, 11, 469–472, doi:10.3762/bjoc.11.52

• synthesis; nucleic acids; nucleoside-5’-diphosphate; phosphorylation; Introduction Nucleoside-5'-phosphates are key to many mechanistic studies and chemical biology applications [1][2][3]. Synthetic approaches towards nucleoside-5'-phosphates are well-established [4], however, the methods tend to be

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• of 5.0–40 μM. The synthesized compounds do not show any antiviral activity. Keywords: antitumor activity; click chemistry; 1,3-dipolar cycloaddition; nucleic acids; 2’-oxa-3’-aza-4’a-carbanucleoside analogs; Introduction Synthetic modified nucleosides are of great interest as potential new lead

TEMPO-derived spin labels linked to the nucleobases adenine and cytosine for probing local structural perturbations in DNA by EPR spectroscopy

• Dnyaneshwar B. Gophane and
• Snorri Th. Sigurdsson

Beilstein J. Org. Chem. 2015, 11, 219–227, doi:10.3762/bjoc.11.24

• paired with A, G, C or T in a DNA duplex. UA and UC had similar mobility order for the different base pairs, with the lowest mobility when paired with C and the highest when paired with T. Keywords: aminoxyl radical; ESR spectroscopy; nitroxide; nucleic acids; site-directed spin labeling (SDSL); spin

• labels; structure-dependent dynamics; Introduction The knowledge about structures and conformational dynamics of nucleic acids, as well as other biomolecules, is essential to understand their biological functions, including interactions with other molecules. The exact atom-to-atom structural information

• scattering is also frequently used to study global structures of large molecules and molecular assemblies [36][37][38][39]. Local structural perturbations in nucleic acids can be studied with some of the aforementioned techniques. For example, NMR has been used to study hydrogen-bonding interactions [11][40

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• barrier was found to be high as no epimerization was detected up to 150 °C, and consistent with this, density functional theory calculations give an inversion barrier of over 40 kcal/mol. Keywords: acylphosphine; acyl phosphite; chiral; DFT; NMR; nucleic acids; oligonucleotides; Introduction Antisense

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• relatively rigid molecular and supramolecular systems. These systems mainly consist of peptides and proteins (e.g., scleroproteins, globular proteins, and membrane proteins), lipids (e.g., biological membranes), carbohydrates (e.g., cellulose) and nucleic acids (DNA, RNA). The impressive performance of the

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues. Keywords: backbone modifications; DNA; nucleic acids; oligonucleotides; stereoselective synthesis; zwitterions; Introduction

• Oligonucleotides are important agents for a number of biomedical applications [1]. Thus, they are employed to exert antigene [2] or antisense [3] mechanisms as well as to trigger or inhibit RNA interference [4]. The capability of sequence-specific molecular recognition is a striking feature of nucleic acids, but

• to develop oligonucleotide-based drug candidates or biomedical chemical probes [5][6]. Native nucleic acids are connected by phosphate diesters as linking units, thus leading to a polyanionic backbone structure. Implications of this characteristic feature of nucleic acid architecture have been

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

• ligand-ILPR complexes are different from the ones observed with other native quadruplex-forming DNA sequences. Keywords: DNA ligands; fluorescent probes; ILPR; nucleic acids; quadruplex DNA; Introduction The “insulin-linked polymorphic region” (ILPR) is a physiologically relevant G-rich DNA sequence

• (ACAG4TGTG4ACAG4TGTG4)], has parallel and antiparallel quadruplex forms that coexist under physiological conditions (Scheme 1) [9]. Notably, the biological relevance of ILPR quadruplexes has been suggested considering recent discoveries on the influence of quadruplex formation on the function of nucleic acids and the

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

• improved synthetic approaches. Keywords: ds-DNA and ds-RNA binding; intercalation; minor groove binding; nucleic acids; organic synthesis; phenanthridine; phenanthridinium; Introduction The search for therapeutic agents of the phenanthridine type has increased when the outstanding trypanocidal activity

• polynucleotides. Among several examples, the most intriguing pH controlled binding of nucleotides and nucleic acids showed bis-phenanthridine triamine [59] (8, Scheme 22). Compound 8 intercalated with only one phenanthridinium subunit into all ds-DNA and ds-RNA, while additional interactions of the other subunit

Nucleic acid chemistry

• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2014, 10, 2928–2929, doi:10.3762/bjoc.10.311

• Hans-Achim Wagenknecht Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany 10.3762/bjoc.10.311 Keywords: nucleic acids; Since the discovery of the structure of the DNA double helix in 1953 by Watson and Crick [1], we know that DNA

Detonation nanodiamonds biofunctionalization and immobilization to titanium alloy surfaces as first steps towards medical application

• Juliana P. L. Gonçalves,
• Afnan Q. Shaikh,
• Manuela Reitzig,
• Daria A. Kovalenko,
• Jan Michael,
• René Beutner,
• Gianaurelio Cuniberti,
• Dieter Scharnweber and
• Jörg Opitz

Beilstein J. Org. Chem. 2014, 10, 2765–2773, doi:10.3762/bjoc.10.293

• regioselective partial incorporation of biofunctional molecules into anodically grown oxide layers. The authors electrochemically immobilized nucleic acids on titanium alloys for its surface modification with bioactive molecules [21][22][23][24][25], as, e.g., oligonucleotides and RGD peptide conjugates, for

Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

• Kayoko Hayashida,
• Taishi Higashi,
• Daichi Kono,
• Keiichi Motoyama,
• Koki Wada and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2014, 10, 2756–2764, doi:10.3762/bjoc.10.292

• ][15], protein drugs [16][17], and nucleic acids [18][19][20]. We have also developed a number of PPRXs with various drugs or drug carriers and utilized them as controlled release systems. For example, γ-CD formed PPRX with coenzyme Q10, improving the solubility and bioavailability of coenzyme Q10 [21

• delivery of anticancer drugs [28]. PEG-LP encapsulating DOX is commercially available as DOXIL/CAELYX® [28]. In addition, PEG-LPs are also utilized as long-circulating drug carriers for protein drugs and nucleic acids [37][38]. Thus, PEG-LPs are representative drug carriers and CD PPRXs of PEG-LPs could be

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• -intermediates in DNA- and RNAzymes via an efficient and straightforward domino carboxamidation reaction. Keywords: amino acids; bioorganic chemistry; carboxamidation reaction; chemically modified; DNA nucleosides; nucleic acids; Introduction For decades DNA has been known as the carrier of the genetic

• predictable and well-investigated structure, the strength of nucleic acids for a series of applications such as DNA and RNA based drugs [7], drug delivery systems [8][9], DNA-biosensors [10][11] and potential catalysts has now firmly been recognized. Rather than using unmodified oligonucleotides, providing

• catalysts, also called DNAzymes [15][16][17] and RNAzymes [10][16][18][19][20][21], respectively. Most catalytic nucleic acids are generated using the SELEX (Systematic Evolution of Ligands by EXponential enrichment) protocol [22][23][24][25] that generates a library of potential catalysts, which are then

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

• transferred to artificial systems like peptide nucleic acids (PNA) [33] and extensively used to mimic biological processes [34][35] or to generate functional materials [36]. Host–guest chemistry has been studied in the field of sequence-specific molecular recognition as well. The selective recognition of