Artificial nucleobase

The final class of fluorinated artificial nucleobases are non-hydrogen-bond-ing isosteres of the natural bases, first described by Kool. The first such... 

The next possible objective is to incorporate increasing numbers of metal ions into DNA and to arrange metals heterogeneously using DNA templates possessing more than two different kinds of artificial nucleobases aligned in a programmable manner. 

Pyrimidine nucleoside bases and purines Artificial nucleobases for hole transport 07Y204. 

Other fluorophores used include thiazole orange (91) used as an artificial nucleobase, to label aptamers, and with two of the dyes attached to the C5 position of dC to act as a sensitive probe for oligonucleotide hybridisation.Various fluorescein derivatives have been used, including a novel fluorescein phosphoramidite that has been described, and a novel dC-modified derivative as well as some modifications that are formed during oligonucleotide synthesis with the fluorescein HEX. Other derivatives have been used to investigate DNA hybridisation under... 

Incorporation of artificial nucleobases into oligodeoxynucleotides using phos-phoramidite derivatives of the nucleosides can be carried out with standard protocols using an automated DNA synthesizer. The first example of metal-mediated... 

Incorporation of an artificial flavin nucleobase and of a cyclobutane pyrimidine dimer building block into DNA DNA double strands, DNArPNA hybrid duplexes, and DNA-hairpins, provided compelling evidence that an excess electron can hop through DNA to initiate dimer repair even at a remote site. The maximum excess electron transfer distance realised so far in these defined Donor-DNA-Acceptor systems is 24 A. New experiments are now in progress to clarify whether even larger transfer distances can be achieved. 

The water-soluble compound 2-amino[l,8]naphthyridine is a novel DNA-binding photosensitizer, which may be employed for the one-electron oxidation of DNA. It is also reported to be an excellent chromophore for the design of artificial electron-accepting nucleobases <1999TL6029>. 

Artificial chemical systems capable of Darwinian evolution have also been prepared from artificial laboratory genetic systems. Such systems were created in the laboratory by using an artificial DNA that contained six nucleotide letters rather than the four in standard terran DNA.6,7 These were chosen from the structures shown in Figure 4.1. The artificial systems can support the basic elements of Darwinian evolution (reproduction, mutation, and inheritance of mutated forms) even if the enzymes that support the evolution of artificial genetic systems are the natural terran enzymes that have evolved for billions of years to handle standard nucleobases. 

Recent reports indicate that divalent transition metal ions, such as Cu +, forming links between two artificial hydroxypyridone nucleobases can efficiently replace the hydrogen bonding between natural nucleobases, A-T and G-C, in oligonucleotides. Such artificial metal-mediated base pairs results in a moderate increase in the thermal stability of the duplex. They could lead to nucleic acid materials with novel chemical and physical properties. Such ohgonucleotide derivatives are of interest for the design of biosensors, nanomolecular wires, and switches. 

This helicate formation mechanism can be extended to interactions with other materials. In the example shown in Fig. 4.2, hgands carrying nucleobases are used. The helicate forms a helical structure similar to the double helix of DNA, where the nucleobases in the helicate are on the outside of the helix. This helixate can form complexes with actual nucleic acid through complementary base pairing. The artificial supramolecular complex can read the programs of naturally-occurring molecules. 

Figure 13.1 Cu2+-mediated DNA duplex formation from two artificial oligonucleotide strands bearing one to five hydroxypyridone nucleobases.

In vitro selection (SELEX, Systematic Evolution of Ligands by Exponential Enrichment) has been employed for over a decade to evolve aptamers and artificial ribozymes with various catalytic functions [169, 170]. However, nucleic acids are, in contrast to proteins, limited to the four nucleobases, thus occupying a more narrow chemical space, which can limit successful SELEX experiments against particular targets. Modified nucleosides in nucleic acid libraries are useful tools in aptamer SELEX to expand the chemical space of DNA [171-174]. 

Hirao I, Kimoto M, Yamashige R (2012) Natural versus artificial creation of base pairs in DNA origin of nucleobases from the perspectives of unnatural base pair studies. Acc Chem Res 45( 12) 2055-2065. doi 10.1021/ar200257x... 

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