An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• information. It plays key roles in replication, transcription, protein-coding and cell integrity as well as in carrying the genetic blueprint for inheritance. The DNA–protein interactions involve high fidelity protein readout of the base edges exposed in the major and minor grooves of the DNA. Such

• ]. Gottesfeld et al. synthesized a series of Py/Im HP-polyamide–DNA alkylator (chlorambucil) (HP-Chl) conjugates in order to bind and alkylate within the HIV-1 promoter region, thereby blocking HIV-1 replication and screened them against human colon carcinoma cell lines [74][75]. It has been observed that

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• stabilized complex prevents the re-ligation step of DNA, catalyzed by topo I, resulting in DNA damage and therefore cell death (apoptosis). CPT is predominantly cytotoxic during the S phase replication of DNA because of the collision of the replication fork with the cleavable complex, converting the single

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• importance for regulating molecular properties like polarizability [1] and in various biochemical processes, including protein folding [2] and stability [3], replication of DNA and RNA [4], enzyme catalysis [5], proton relay mechanism [6], and drug delivery [7]. Energy decomposition analysis (EDA) schemes

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

• -Me analogues of pyrrolo- and imidazo[2,1-f][1,2,4]triazine C-nucleosides using a 2'-β-Me lactone that mimic adenosine and guanosine (12–19, Figure 8) [71][72]. The adenine analogues of pyrrolo- and imidazo[2,1-f][1,2,4]triazine were active as nucleosides in HCV1b RNA replication assays, and as

• triphosphates they inhibit the NS5B polymerase as did the triphosphates of the guanosine analogues [71]. The library of adenosine analogues was further expanded by introducing functional groups at C7 (16–19), which exhibit potent activity in RNA replication assays, with the carboxamide group in particular

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• macromolecules such as mRNA and DNA [10][11]. More precisely, anthracyclines act as topoisomerase II toxins inhibiting DNA transcription and replication. They stabilize a DNA topoisomerase-II intermediate in which the DNA strands are separated and a specific tyrosine residue of the topoisomerase II is covalently

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• suggest that enzyme-free primer extension is a more powerful reaction than previously thought. Keywords: base pairing; DNA; enzyme-free primer extension; nucleotides; oligonucleotides; replication; RNA; Introduction Replication of genetic information is critical for all living systems. In the cell, this

• process is catalyzed by enzymatic machineries that have polymerases at their core [1]. Polymerases catalyze not only the replication of DNA, but are also involved in repair and transcription of genes [2]. Considering that enzymes catalyze processes that lead to protein synthesis, it is reasonable to ask

• what started replication when life emerged on planet Earth. A solution to the chicken/egg dilemma of replication might be found in RNA, as oligo- and polyribonucleotides can encode genetic information and can catalyze biochemical reactions as ribozymes. More than 30 years ago, it was observed that RNA

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

• PNATAR fragment directed against the TAR RNA region of the HIV genome conjugated to TPP inhibited HIV replication in CEM cell lines with an IC50 of 1 μM, while the unconjugated 16-mer PNATAR was inactive in these tests. The anti-HIV activity confirmed that the PNATAR was not sequestered in mitochondria

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -aminopyrazolo[1,5-a]pyrimidine derivatives 155 (Scheme 43). All the synthesized compounds were screened for their anti-HIV activities in MT4 cell cultures and compound 155 (R1 = 2,4,6-trimethyl and R2 = 4-cyano) was found as most inhibiting for HIV-1 replication having an EC50 = 0.070 μM and the SI (selectivity

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

• and conformational changes using base–base FRET Many biologically important processes such as binding of transcription factors to DNA, polymerase–DNA interactions during replication, gene regulatory systems and structure variation due to changes in conditions (e.g., B-to-Z-form DNA), generally involve

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

• (capacity of self-maintenance, self-replication and evolution under external constraints), should be investigated using a systemic approach where the functionalities in a chemical mixture are derived from the multiple interactions or “interconnected work” that exists between the various chemical processes

• blocks, such as amphiphiles and catalytic and information biopolymers, and the processes linked to protocell replication (see section “iii) Support of functional systems proliferation”) occasionally linked to uptake and conversion of energy from a primary source, such as light. From the evolutionary

• sophisticated organisation of the contemporary one. Support of functional systems proliferation To achieve a “life”-like status, protocells should have been able not only to maintain themselves, but also to reproduce and change (evolve). The reproduction phase involves replication of all its internal content

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

• , what kind of molecule (often, what kind of biopolymer) came first, analysing either the abiotic pathway of synthesis that could have brought it about, or the reactive processes that it could have provoked (i.e., the replication or catalytic processes it hypothetically took part in). Fortunately

• avenues in the field of systems chemistry [1][2]. For instance, although kinetic control mechanisms must play a central part in the explanation, dynamic kinetic stability [63] is not the answer (because replication is not all what matters for evolution, chemical or biological). It is probably too early to

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

• understanding of how life could have emerged from molecular building blocks and what is needed to create a minimal form of life in the laboratory. Keywords: autocatalysis; open-ended evolution; origin of life; self-replication; synthetic life; Introduction Mankind has always pondered upon its own existence

• information only appeared later. These self-replicating molecules carry hereditary information in the form of their molecular structure that can be passed on to successive generations. If mutations occur during the replication process, genetic information can change from one generation to the next. Natural

• provide an insight into the historical background and recent developments in the field of in vitro evolution of self-replicating molecules. To do so, we will first cover a few important principles of Darwinian evolution and will show how these concepts apply to the case of molecular self-replication. This

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

• replication processes (making exact copies), a metabolic system must have reproduced (making similar copies), progressively increasing the accuracy of its pathways before allowing a spin-off system to initiate replication. Here I try to pursue this track and go beyond standard views of what life is, and how

• metabolic cycles, but, as noticed by Dyson, this is an unstable way to keep traces of past events [1]. A further memorisation step, at the origin of replication, must have followed the reproduction of metabolism. Concretely, in living cells the replicated substance of the blueprint memory of the cell is its

• as a template for the daughter, as in nucleic acids, for example. In fact, the entity that is replicated is not a protein complex but an algorithm of construction. Hence, in this particular instance, replication is not a protein-replication system, nor is it directly associated to nucleic acids used

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

• treatment of HIV infection. β-D-Glucose coated AuNPs have been decorated with the antiviral drugs abacavir (ABC) and lamivudine (3TC) and used as delivery systems. These co-drug structures were able to release the drugs in acidic conditions to inhibit viral replication in cellular assays [91]. GAuNPs

Use of costic acid, a natural extract from Dittrichia viscosa, for the control of Varroa destructor, a parasite of the European honey bee

• Kalliopi Sofou,
• Demosthenis Isaakidis,
• Apostolos Spyros,
• Anita Büttner,
• Athanassios Giannis and
• Haralambos E. Katerinopoulos

Beilstein J. Org. Chem. 2017, 13, 952–959, doi:10.3762/bjoc.13.96

• mass spectra using the NIST 64 and NIST 120 GC–MS libraries and the comparison of their retention times with those of reference. Screening tests. The experiment was conducted in a completely randomized design under laboratory conditions in five replications. In each replication 20, 60, or 100

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

• possibilities for variation are indeed a requirement for systems to undergo open-ended evolution [66]. The storage of genetic information as a sequence in a polymer associated with template replication through base-pairing constitutes an efficient system to ensure evolvability. It is that evolvability which

• 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

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• , which inhibit HCV replication [9][10] (Figure 1). First publications concerning the preparation of 1-indanones appeared in the 1920s and since then this field has been intensively developed [11]. A huge interest in 1-indanones and their derivatives resulted in a considerable number of papers concerning

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

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

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• be optimised alongside mixing performance [46], and in nanotechnology, where shaking can be used to modulate aggregation so as to favour particular nanostructures [47][48]. Otto and co-workers have investigated the influence of mechanical forces on reactivity in the context of self-replication by

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• transglycosylation during peptidoglycan synthesis [23], the same step inhibited by vancomycin [24]. Enduracidin A (7) and B (8) also exhibited inhibition of avian myeloblastosis virus reverse transcriptase but did not suppress replication of HIV cells [25]. Enduracidin A (7) and B (8) have been produced by

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

• replication and folate metabolism [21]. Promising candidates meeting the requirements for new drugs are nucleoside antibiotics, i.e., uridine-derived compounds that address the enzyme translocase I (MraY) as a novel target, thereby interfering with a membrane-associated intracellular step of peptidoglycan

• essential for bacterial survival or growth and offers selectivity to strike only bacterial cells (without cytotoxicity to human cells). There are mainly four classical target processes for antibiotics: bacterial cell wall biosynthesis, bacterial protein biosynthesis, DNA replication and folate metabolism

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

• , for example, the ends of DNA double helices, replication forks, or abasic sites. My original research proposal was submitted August 16, 1983 and was entitled “Synthesis of a Rigid ‘Molecular Tweezer’ with Novel DNA Binding Potential.” The name “molecular tweezer” was inspired by Howard Whitlock’s 1978

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

• largest classes of drugs. Most antimetabolite drugs are nucleoside derivatives that substitute for endogenous nucleosides and prevent DNA and protein replication [1]. Many of the drugs described by the World Health Organization as "essential medicines" are nucleoside derivatives [2] and nearly 20% of all

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

• different biological effect with respect to 2’-oxa-3’-aza-4’a-carbanucleosides devoid of the triazole unit, such as compounds 2 and 8, which are endowed with antiviral activity, but do not show any cytotoxicity The ability of compounds 13a–g and 14a–g to interfere with the replication of different DNA and