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A deeper investigation of the chemistry that occurs on the newly discovered epigenetic DNA bases 5-hydroxymethyl-(hmdC), 5-formyl-(fdC), and 5-carboxy-deoxycytidine (cadC) requires chemical tool compounds, which are able to dissect the different potential reaction pathways in cells. Here we report that the 2′-(R)-fluorinated derivatives F-hmdC, F-fdC, and F-cadC, which are resistant to removal by base excision repair, are good substrates for DNA polymerases and TET enzymes. This result shows that the fluorinated compounds are ideal tool substances to investigate potential C–C-bond cleaving reactions in the context of active demethylation. [ABSTRACT FROM AUTHOR]

Real-time enzymatic studies are gaining importance as their chemical and technical instrumentation improves. Here we report the efficient synthesis of γ-alkyne modified triphosphate amidates that are converted into a variety of γ-fluorophore labeled triphosphates by Cu(i) catalyzed alkyne/azide click reactions. The synthesized triphosphates are incorporated into DNA by DNA polymerases. [ABSTRACT FROM AUTHOR]

The development of metal base pairs is of immense importance for the construction of DNA nanostructures. Here we report the synthesis of a biaryl pyrazole–phenol nucleoside that forms in DNA a stable self-pair upon complexation of a Cu(ii) ion. A sequence with five consecutive pyrazole nucleotides allows the complexation of five Cu(ii) ions in a row. [ABSTRACT FROM AUTHOR]

Modern life requires the translation of genetic information - encoded by nucleic acids - into proteins, which establishes the essential link between genotype and phenotype. During translation, exclusively l-amino acids are loaded onto transfer RNA molecules (tRNA), which are then connected at the ribosome to give homo-l-proteins. In contrast to the homo-l-configuration of amino acids and proteins, the oligonucleotides involved are all d-configured (deoxy)ribosides. Previously, others and us have shown that if peptide synthesis occurs at homo d-configured oligonucleotides, a pronounced l-amino acid selectivity is observed, which reflects the d-sugar/l-amino acid world that evolved in nature. Here we further explore this astonishing selectivity. We show a peptide-synthesis/recapture-cycle that can lead to a gradual enrichment and hence selection of a homo-l-peptide world. We show that even if peptides with a mixed l/d-stereochemistry are formed, they are not competitive against the homo-l-counterparts. We also demonstrate that this selectivity is not limited to RNA but that peptide synthesis on DNA features the same l-amino acid preference. In total, the data bring us a step closer to an understanding of how homochirality on Earth once evolved., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

acp3U is a hypermodified base that is found in the tRNAs of prokaryotes and eukaryotes and also in the ribosomal RNA of mammals. Its function has so far been unknown but it is speculated that acp3U complexes Mg ions, which may contribute to the stabilization of the RNA structure. As a hypermodified base in which a nucleoside is covalently connected to an amino acid, acp3U is a natural nucleoside between genotype and phenotype and hence is also of particular importance for theories about the origin of life. Herein, we report the development of a phosphoramidite building block and of a solid phase protocol that allows synthesis of RNA containing acp3U.

Herein, we report a new prebiotically plausible pathway towards a pyrimidine nucleobase in continuous manner. The route involves simultaneous methylation and carbamoylation of cyanoacetylene-derived α,β-unsaturated thioamide with N-methyl-N-nitrosourea (MNU) in aqueous media. This provides S-methylpyrimidinone in one-pot, which can be converted into a variety of 4-substituted pyrimidine nucleobases including cytosine and uracil.

RNA contains methylated A-base derivatives. A methylation to m 6 A and then demethylation regulate homeostasis in mRNA. It is assumed that m 6 A is mainly demethylated by the α-ketoglutarate dependent oxidase ALKBH5. Here we show that ALKBH5 also demethylates the dimethylated adenosine m 6 2 A, which is a non-canonical base present in ribosomal RNA.

The DNA structure is an ideal building block for the construction of functional nano-objects. In this direction, metal coordinating base pairs (ligandosides) are an appealing tool for the future specific functionalization of such nano-objects. We present here a study, in which we combine the metal ion coordinating pyrazole ligandoside with the interstrand crosslinking salen ligandoside system. We show that both ligandosides, when combined, are able to create stable multi-copper ion complexing DNA double helix structures in a cooperative fashion.

The radical SAM enzyme, spore photoproduct lyase, requires an H-atom transfer (HAT) pathway to catalyze DNA repair. By rational engineering, we demonstrate that it is possible to rewire its HAT pathway, a first step toward the development of novel catalysts based on the radical SAM enzyme scaffold.

The spore photoproduct lyase is a radical SAM enzyme, which repairs 5-(α-thyminyl)-5,6-dihydrothymidine. Here we show that the enzyme establishes a complex radical transfer cascade and creates a cysteine and a tyrosyl radical dyade to establish repair. This allows the enzyme to solve topological and energetic problems associated with the radical based repair reaction.

Recently new lysine modifications were detected in histones and other proteins. Using the pyrrolysine amber suppression system we genetically inserted three of the new amino acids ε-N-propionyl-, ε-N-butyryl-, and ε-N-crotonyl-lysine site specifically into histone H3. The lysine at position 9 (H3 K9), which is known to be highly modified in chromatin, was replaced by these unnatural amino acids.

RNA nucleosides are often naturally modified into complex non-canonical structures with key biological functions. Here we report LC-MS quantification of the Ar(p) and Gr(p) 2'-ribosylated nucleosides in tRNA using deuterium labelled standards, and the first detection of Gr(p) in complex fungi., (© The Royal Society of Chemistry 2011)

A new photoinducible single electron donor has been developed, which, when linked to thymidine, is shown to be an efficient ground state reducing agent in DNA; the donor can be activated at wavelengths where standard DNA does not absorb.

The spore photoproduct is a unique photolesion, formed in spores upon irradiation with UV light; to investigate the properties of spore photoproduct containing DNA we have synthesized 5S and 5R lesion analogs and incorporated them into DNA.

We present a new type of azide-functionalized gold nanoparticle and their coupling to an alkyne-modified DNA duplex using the copper(I)-catalyzed Huisgen cycloaddition ('click chemistry'), resulting in a chain-like assembly of nanoparticles on the DNA template.

Modified nucleosides in tRNAs play an important role in the translational process. They fine tune the codon-anticodon interactions and they influence the folding and stabilisation of the tRNA structure. Herein, we present a novel synthetic route to the highly modified nucleosides PreQ(0) and archaeosine. The synthesis involves coupling of a protected 7-cyano-7-deazaguanosine nucleobase with a TBDMS and isopropylidene protected chloro-ribose unit yielding the PreQ(0) nucleoside after deprotection. This PreQ(0) nucleoside is then used as the starting material for the synthesis of archaeosine providing the first total synthetic access to this hypermodified RNA nucleoside.

The spore photoproduct lyase is a Fe-S/AdoMet DNA repair enzyme, which directly repairs spore lesions, induced by UV irradiation of spores, using an unknown radical mechanism. The air sensitive radical SAM enzyme was for the first time challenged with synthetically pure substrates. It was found that the enzyme recognizes a synthetic 5S-configured spore lesion without the central phosphodiester bond. The 5R-configured lesion is in contrast to current belief not a substrate.

Thietanes were used in the past as mimics for an unstable oxetane intermediate formed during the repair of mutagenic (6-4) lesions. The thietane derivatives were found to be not repaired, raising the question of how well thietanes are cleaved by single electron donation compared to oxetanes. We have prepared two flavin-containing oxetane and thietane model compounds for the (6-4) photolyase catalyzed repair process and we show that both are efficiently cleaved by a reduced and deprotonated flavin. Thietanes are therefore excellent models. The lack of their repair can be attributed to lack of binding.

Investigation of hole or excess electron hopping in DNA is mostly performed based on yield studies, in which an injector modified DNA duplex is irradiated to continuously inject either holes or electrons into the duplex. Observed is a chemical reaction of a "probe" molecule, which can be either one of the two purine bases or a different trap molecule positioned at various distances. The next step in the field will be the direct time resolution of the hole or electron transfer kinetics in DNA. Herein we describe the development of defined donor-DNA-acceptor systems, with properties that may allow time resolved electron and hole transfer studies in stably folded DNA structures.

The transfer of an excess electron through DNA was investigated with DNA hairpins, which contain a flavin cap functioning as an electron donor. A thymine dimer with an open backbone acts as the electron acceptor. The dimer translates the electron capture into a strand break, which is readily detectable by HPLC. Analysis of four hairpins, in which the distance between the flavin donor and the dimer acceptor was systematically increased, revealed a flat distance dependence of the repair efficiency supporting the view that excess electrons hop through DNA using intermediate A-T base pairs as temporary charge carriers.

DNA is currently explored as a new material for functional, molecular nano-architectures. In this respect, one major question is to transform DNA into a conducting material which has the potential for self-assembly into electronically active networks. The article covers recent insight into how DNA transports positive (holes) and negative (excess electrons) charges. It was found that holes move through DNA over significant distances using a G- and to a lesser extent also A-based hopping mechanism. EPR studies and recent investigations with model systems show that excess electrons can also hop through the duplex. The second part of the article describes how DNA is currently modified, particularly coated with metals, in order to increase the conductivity.