Artificial DNA Made Exclusively of Nonnatural C-Nucleosides with Four Types of Nonnatural Bases

Doi, Yasuhiro; Chiba, Junya; Morikawa, Tomoyuki; Inoûye, Masahiko

doi:10.1021/ja801058h

Cited by 66 publications

(55 citation statements)

References 102 publications

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“…Other research groups have recently adopted an enlargedbase-pair strategy as well. 14-16 In our approach, benzopyrimidines pair with purines and benzopurines 17 with pyrimidines, yielding up to eight letters of information encoding capability. 5,7 The study of this nonnatural genetic set gives basic insight into the chemical, structural, and biophysical properties that govern encoding and transmission of genetic information.…”

Section: Introductionmentioning

confidence: 99%

Encoding Phenotype in Bacteria with an Alternative Genetic Set

et al. 2011

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An unnatural base-pair architecture with base pairs 2.4 Å larger than the natural DNA-based genetic system (xDNA) is evaluated for its ability to function like DNA, encoding amino acids in the context of living cells. xDNA bases are structurally analogous to natural bases but with benzene added, increasing their sizes and resulting in a duplex that is wider than native B-DNA. Plasmids encoding green fluorescent protein were constructed to contain single and multiple xDNA bases (as many as eight) in both strands, and were transfected into E. coli. Although yielding fewer colonies than the natural control plasmid, in all cases in which a modified plasmid (containing one, two, three, or four consecutive size-expanded base pairs) the correct codon bases were substituted, yielding green colonies. All four xDNA bases (xA, xC, xG, xT) were found to encode the correct partners in the replicated plasmid DNA, both alone and in longer segments of xDNA. Controls with mutant cell lines having repair functions deleted were found to express the gene correctly, ruling out repair of xDNA and confirming polymerase reading of the unnatural bases. Preliminary experiments with polymerase deletion mutants suggested combined roles of replicative and lesion-bypass polymerases in inserting correct bases opposite xDNA bases and in bypassing the xDNA segments. These experiments demonstrate a biologically functioning synthetic genetic set with larger-than-natural architecture.

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Section: Introductionmentioning

confidence: 99%

Encoding Phenotype in Bacteria with an Alternative Genetic Set

et al. 2011

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“…Other examples of new DNA-like genetic architectures have been described, including base pairs with four hydrogen bonds 46 and bases with ethynyl homologation. 47 Although such fully unnatural designs might generally be expected to interact with natural enzymes poorly, experiments show that this might not always be the case. For example, our laboratory demonstrated that xDNA can be replicated in vitro by some DNA polymerases.…”

Section: Synthetic Biologymentioning

confidence: 99%

Chemistry of nucleic acids: impacts in multiple fields

Khakshoor

Kool

2011

Chem. Commun.

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Research in nucleic acids has made major advances in the past decade in multiple fields of science and technology. Here we discuss some of the most important findings in DNA and RNA research in the fields of biology, chemistry, biotechnology, synthetic biology, nanostructures and optical materials, with emphasis on how chemistry has impacted, and is impacted by, these developments. Major challenges ahead include the development of new chemical strategies that allow synthetically modified nucleic acids to enter into, and function in, living systems.

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“…Taking a related expanded-size approach, Inouye has recently designed an artificial genetic set composed entirely of nonnatural C-glycosides in which added length is conferred by an ethynyl group [59]. The recognition of these bases relies on six-member heterocycles with Watson-Crick-like hydrogen-bonding faces (iG*:iC*, three hydrogen bonds, A*:T* two hydrogen bonds), linked to the C1′ of deoxyribose by the ethynyl spacer.…”

Section: Why Modify Dna Bases?mentioning

confidence: 99%

Redesigning the Architecture of the Base Pair: Toward Biochemical and Biological Function of New Genetic Sets

Krueger

Kool

2009

Chemistry & Biology

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Recognition of the nucleic acid bases within the DNA scaffold comprises the basis for transmission of genetic information, dictating protein and cell assembly, organismal development, and evolution. Driven in part by the need to test our current understanding of this information transfer, chemists have begun to design and synthesize nonnatural bases and base pair structures to mimic the function of DNA without relying on Nature’s purine-pyrimidine base pair scaffold. Multiple examples have been recently described of new genetic architectures that self-assemble stably and sequence specifically in vitro, and experiments with polymerases in vitro show that at least isolated unnatural base pairs can be replicated as well. Moreover, recent experiments with unnatural bases in bacterial cells have demonstrated surprisingly efficient reading of the chemical information. This suggests the future possibility of redesigning and replacing the chemical information of an evolving cell while retaining biological function. Such unnatural base pair components, whether recognized by nature or not, are already proving useful in biotechnology. In addition to practical applications, this chemical approach also gives basic insight into the forces and mechanisms that govern DNA structure and replication.

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Artificial DNA Made Exclusively of Nonnatural C-Nucleosides with Four Types of Nonnatural Bases

Cited by 66 publications

References 102 publications

Encoding Phenotype in Bacteria with an Alternative Genetic Set

Encoding Phenotype in Bacteria with an Alternative Genetic Set

Chemistry of nucleic acids: impacts in multiple fields

Redesigning the Architecture of the Base Pair: Toward Biochemical and Biological Function of New Genetic Sets

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