Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• . Mechanochemistry has also found recent attention in materials chemistry and API formulation during which rearrangement of non-covalent interactions give rise to functional products. However, this has been known to nucleic acids science almost since its inception in the late nineteenth century when Miescher

• contribution of mechanochemistry (and specifically, ball milling) to the isolation of biologically active materials derived from nuclei by grinding will also be outlined. Finally non-covalent associative processes involving nucleic acids and related materials using mechanochemistry will be described

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• Satu Mikkola Tuomas Lonnberg Harri Lonnberg Department of Chemistry, University of Turku, FIN-20014 Turku, Finland 10.3762/bjoc.14.68 Abstract Nucleic acids that store and transfer biological information are polymeric diesters of phosphoric acid. Cleavage of the phosphodiester linkages by protein

• studies with small molecular phosphodiesters. Keywords: Cleavage; DNA; kinetics; mechanism; RNA; Introduction Nucleic acids are polymeric diesters of phosphoric acid that store and transfer biological information. In biological systems, the diester linkages bridging 3´-O of one nucleoside to the 5´-O of

• computational methods [11][12][13][14]. Still, experimental studies with small molecular model compounds play an essential role in mechanistic studies of the enzymatic cleavage of nucleic acids. With small molecules, the importance of various elementary processes, such as proton transfer and metal ion binding

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• synthesis; modular synthesis; Introduction Nucleic acids form the genetic blueprint for all living organisms and are involved with a wide range of cellular functions [1][2][3][4][5][6][7][8][9]. Modifications to their chemical structure can have profound effects on structure and function of enzymes, cells

• and supramolecular complexes [10][11][12][13][14][15][16][17][18][19][20][21][22]. Nucleic acids are composed of a monomeric nucleoside unit that features an aromatic nitrogenous moiety (a nucleobase) connected to a pentose sugar, which in turn is attached to a phosphate group (Figure 1) [7]. The

• acids. Shown is the monomeric building block of nucleic acids. Changes to the nucleotide structure can affect molecular recognition, as well as structure and function. Formation of oxocarbenium ion during glycosidic bond cleavage in nucleosides [31]. The extent of leaving group stabilization and

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

• group; oligonucleotide prodrugs; reduction-responsive; stimuli-responsive nucleic acids; thermolytic prodrugs; Introduction For past decades, oligonucleotide-based therapies have been widely developed using short synthetic oligonucleotides (ONs) and their chemically modified mimics as powerful tools to

• such as gene regulation is to circumvent the poor chemical stability of nucleic acids in biological media due to their low resistance to nucleases and to overcome their low cell uptake due to their polyanionic nature. In the present review, we aimed to identify various ON prodrugs that are responsive

• nucleic acids (PNAs), a lipophilic triphenylphosphonium (TPP) cation was attached to the N-terminal extremity of a PNA through a biodegradable carbamate linker containing a disulfide bridge (Scheme 4B) [20]. It was shown that such PNA conjugates entered cells rapidly and efficiently. Furthermore, a 16-mer

Fluorogenic PNA probes

• Tirayut Vilaivan

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

• to specific biomolecular targets, including nucleic acids as well as non-nucleic acid targets, such as proteins and small molecules, have applications in various important areas. These include diagnostics, drug development and as tools for studying biomolecular interactions in situ and in real time

• attention has been paid to the recognition element. Peptide nucleic acids (PNA) are DNA mimics with several favorable properties making them a potential alternative to natural nucleic acids for the development of fluorogenic probes, including their very strong and specific recognition and excellent chemical

• vivo. For nucleic acids, the latter valuable information cannot be obtained by sequencing despite the tremendous advances in the field in recent years [1]. Accordingly, fluorescent oligonucleotide probes are still one of the most important tools not only for the detection of nucleic acids, but also

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

• . Base–base FRET has been around for less than a decade, only in 2017 expanded beyond one FRET pair, and represents a highly promising structure and dynamics methodology for the field of nucleic acids. Here we bring up its advantages as well as disadvantages and touch upon potential future applications

• . In this review we will focus on the FRET between fluorescent base analogues, i.e., base–base FRET, the theory behind it, the increased accuracy in orientation factor κ2 as an effect of their position inside the base-stack, other advantages and disadvantages compared to FRET in nucleic acids using

• by Lin et al. of 22% [41]. Synthesis of adenine analogues for base–base FRET Buhr et al. were interested in developing modified adenosines that could thermodynamically stabilize double-stranded nucleic acids [51]. In 1999, a short synthesis article regarding quadracyclic adenine, qA, was published

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• non-covalent complexes between nucleic acids and small molecules (ligands) is of a paramount significance to bioorganic research. Highly informative methods about nucleic acid/ligand complexes such as single crystal X-ray diffraction or NMR spectroscopy cannot be performed under biologically

• between nucleic acids and small ligands. This tutorial aims to help researchers entering the research field to organize experiments accurately and to interpret the obtained data reliably. Keywords: circular dichroism; emission-based dichroism; groove binding; intercalation; linear dichroism; non-covalent

• interactions; nucleic acids recognition; vibrational circular dichroism; Review 1. Introduction Many biological molecules are chiral and chromophoric among which the most important examples include proteins and nucleic acids. Moreover, the chiral constituents of natural biopolymers are homochiral, e.g

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• infection and persistent inflammation. 2.2. Synthesis of monophosphoryl lipid A (MPLA) as potential vaccine adjuvant In contrast to the attenuated or whole killed vaccines which contain bacterial cell wall components and nucleic acids serving as naturally occurring adjuvants, the subunit vaccines lack these

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

• fluorescence spectroscopy) and theoretical (DFT and TDDFT calculations) methods. Keywords: cyanine dyes; DFT calculations; green synthesis; nucleic acids; thiazole orange; Introduction Since the discovery by Lee and co-workers [1][2] that the old photographic dye thiazole orange, TO, (Scheme 1) has excellent

• moieties is somehow limited [5][6][7]. Such a restriction occurs when TO derivatives bind to nucleic acids by intercalation between the base pairs [6][8] or presumably between individual bases in single-stranded nucleic acids and in both cases a dramatic increase of the fluorescence is observed. The

• been conjugated to a variety of molecules, including peptides [29], proteins [30], DNA [17], and DNA analogues such as peptide nucleic acid (PNA) [16][31]. TO-based chromophores assembled as a structural scaffold inside nucleic acids (TO-tethered nucleic acids) have attracted considerable attention [32

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

• ) N/P ratios were between 0 (pUC19 only) and 27.5 for each AmCD; b) N/P ratios up to 38.5, 60.6 and 49.5 were used. nr Values for the AmCD–Alg interaction. Minimum N/P ratios for complete binding of different forms of nucleic acids. Supporting Information Supporting information features a mechanistic

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

Beilstein J. Org. Chem. 2017, 13, 2671–2681, doi:10.3762/bjoc.13.265

• base pairs reported as yet in parallel-stranded DNA, compares them with their counterparts in regular DNA (where available), and explains the experimental conditions used to stabilize the respective parallel-stranded duplexes. Keywords: DNA; metal-mediated base pairs; nucleic acids; Introduction

• Nucleic acids are increasingly being applied in areas beyond their original biological context, e.g., as a scaffold for the defined spatial arrangement of functional entities [1][2][3]. This often goes along with the formal substitution of a canonical nucleoside (or any other nucleic acid component) by an

• application in metal-mediated base pairing [6][7]. Structural analyses have shown that their formation is possible without major conformational changes of the nucleic acid [8], even though metal-modified nucleic acids may very well adopt non-helical topologies [9]. It is even possible to create DNA duplexes

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• [4], pyrene-modified peptide nucleic acids (PNA) [5], locked nucleic acids (LNA) [6][7], invader LNA [8], and twisted intercalating nucleic acids (TINA) [9]. Furthermore pyrene-modified nucleotides have been used for the construction of DNA-based multichromophore systems [10][11][12][13], as cancer

• chromophores [19][20][21]. This helical twist was evidenced by circular dichroism, in particular a strong bisignate Cotton effect for the DNA-templated pyrene assemblies [19][20]. Figure 1 shows selected examples of pyrene-modified nucleic acids and nucleosides. On the other hand, pyrene–nucleobase conjugates

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

• ; polarity; Introduction Fluorine is a rare element in natural biochemical settings [1]. Notwithstanding several prominent fluoro-organic metabolites in nature [2][3], fluorine is virtually absent from natural biopolymers such as proteins and nucleic acids. Therefore, organofluorine groups lack a natural

• 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

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• mixture of xylo- and ribofuranosides. Separated epimers were further used as sugar precursors for the convergent synthesis of two different types of bicyclic nucleosides which are monomers of oxetano- and locked nucleic acids of medicinal importance [16]. Results and Discussion 4-C-Hydroxymethyl-1,2-O

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• -glycerols [18], indicating that the disparity between gt(+) and gg(−) conformers varies widely by influences from sn-3 groups. Helical properties constitute one of the major factors in determining the molecular chirality [20] of not only proteins and nucleic acids but also simpler biomolecules [17][18][19

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• , modification of bioactive substrates with PEG is well established in drug development, and is also becoming important in the purification of proteins and nucleic acids [1]. Since the first demonstration of PEGylated proteins with altered immunogenicity [2][3], PEG has been heavily investigated for affording

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

• explain its selection for the backbone of nucleic acids. Catalysis support The promotion of some complex catalyses was also shown to occur more readily in the presence of molecular assemblies, that is, in the context of a chemical system. Such effects could be either directly linked to the insertion into

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

• biopolymer apparatus, which essentially consists of proteins and nucleic acids carrying out complementary tasks to orchestrate an intricate and heterogeneous dynamic organisation with surprising robustness. In addition, this organisation always involves an endogenously synthesized boundary that protects

• 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

• evolution (as explained in more detail in [60]). Instead of using compartmentalization simply as a way to segregate populations of nucleic acids (with the aim to avoid problems like parasitism [61]), the idea here is that integrated protocells constitute the actual units of evolutionary change from the very

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• average particle size, distribution and shape. Different kinds of samples beside soluble proteins can be studied by this technique including nucleic acids, protein-based complexes, lipids, membrane proteins and surfactants, glycoproteins, virus, polymers and colloids [78][79]. Proteins: SAXS applied to

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

• it emerged, trying to find the simplest ways forward. I focus on one single question, that of the origin of the coding relationship that links the effectors of life functions (in material, molecular terms, the proteins) to the providers of the memory (the genetic program made of nucleic acids) used

• , this means a machine and a separate program that is run by the machine. Here, I identify the program driving the life of the cell with its genetic program, chemically embodied in its genome based on nucleic acids and I study how the innards of the machine emerged first. I propose that what we currently

• making nucleic acids that carry the program, and the amino acid building blocks making proteins. This has very deep consequences that ask for a thorough and time-consuming study. The abstract process of coding has given Douglas Hofstadter the subject of a book more than six hundred pages long, “Gödel

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

• replication by von Kiedrowski [67], leads to sub-exponential growth. It turns out, at least at this time, that no isolated system able to reproduce itself, presents all of the qualities required for the emergence of life: i.e., the replication of nucleic acids through base-pairing is limited by parabolic

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

• not present in nucleic acids [2][3][4][5]. Although Huisgen described the uncatalyzed reaction yielding 1,2,3-triazoles already in the 1960s [6], the bioorthogonality with respect to proteins and nucleic acids emerged after Sharpless [7] and Meldal [8] had reported that catalysis by Cu(I) enhances not

• structure of double-helical DNA elucidates that the positioning of the fluorophores in the major groove may be improved by inversion of the configuration at the 2’-position of the anchor nucleoside sugar. In fact, arabino nucleic acids are an important class of antisense oligonucleotides [20] since their

• , respectively. This small difference tracks well with the general observation that arabino-configured nucleic acids in general show lower stabilities than the ribo-configured ones. With the attached dyes, the arabino-modified duplexes show a smaller stabilization effect by the dyes than the corresponding ribo

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

• complexes with various biomolecules including lipids, carbohydrates, proteins and nucleic acids. In this section, some biomolecule/CD inclusion complexes are presented. i) Complexation of lipids and consequences Lipids are hydrophobic or amphiphilic molecules very diverse, including, among other fats, waxes

• neglected. Similar conclusions were made by Paal and Szeijtli [103]. iv) Complexation of nucleic acids Nucleic acids are macromolecules, where the monomer is the nucleotide. Each nucleotide has three components: a 5-carbon sugar, a phosphate group, and a nitrogenous base. These nucleotides are joined by

• 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

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• addition of Lambda Protein Phosphatase that removes the phosphate group [42]. It is widely accepted that this reversible process of phosphorylation directs diverse properties of peptides or proteins in nature, ranging from interactions with other proteins and nucleic acids to subcellular localization and

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• are highly reactive compounds that are usually treated with alcohols or amines to give either a new carbonate or a carbamate-linked compound depending on the nucleophile. In one of our earlier reports, polycarbamate nucleic acids were synthesized from p-nitrophenyl carbonates with amines of nucleic