A Parallel Screen for the Discovery of Novel DNA Base Pairs

Yaren, Oezlem; Mosimann, Markus; Leumann, Christian J.

doi:10.1002/anie.201005300

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…In terms of molecular recognition in duplex structures we find in general that the T m -values observed here with the carbocyclic exo-amino nucleosides match well with those observed previously in the parallel screen 25 with the (noncarbocyclic) exo-amino nucleosides. This validates the methodology of the screen and suggests that there are no significant differences in complementary base recognition as a function of whether there is a CH 2 group or an oxygen atom in the five-membered ring.…”

Section: Discussionsupporting

confidence: 90%

“…28 The aromatic amines chosen, namely aniline (AN), naphthalene-1,5-diamine (DAN), benzene-1,3-diamine (DAB), pyridin-3-amine (AP), and 6-aminoflavone (CHR) have been selected from the previously described combinatorial assay. 25 Ozlem (1987)(1988) as a postdoctoral fellow to investigate catalytic antibodies (Prof. Peter G. Schultz). In 1988 he returned to ETH Zürich to start his independent career.…”

Section: Synthesis Of Carbocyclic Exo-amino Nucleosides and Building mentioning

confidence: 99%

“…The fluorescence measurements (Supporting Information) were performed to comply with the measurements of the previous assay. 25 The UV-measurements were carried out to validate the fluorescence measurements. As expected, we found no significant differences between the T m -values determined by the two methods.…”

Section: Pairing Properties Of Oligonucleotidesmentioning

confidence: 99%

“…In this context, we recently developed a combinatorial assay for the discovery of novel base surrogates out of a library of aromatic amines. 25 The assay is based on the reversible formation of hemiaminals of primary aromatic amines with a chemically functional abasic site in the center of a DNA duplex in a parallel fashion. Matches were identified by fluorescence-based thermal melting experiments.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Incorporation into Oligodeoxynucleotides of Carbocyclic exo-Amino Nucleosides

Yaren¹,

Röthlisberger²,

Leumann³

2012

Synthesis

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The preparation of a series of carbocyclic exo-amino nucleosides from selected primary aromatic amines in both the C1¢ aand b-epimeric form as well as the corresponding building blocks for DNA synthesis is described. These nucleosides were incorporated into oligodeoxynucleotides and their base-pairing properties with natural bases and, in part, with themselves investigated. The results obtained confirm that such nucleoside analogues engage in specific interactions with natural nucleotides in DNA duplexes. In addition they can form self-pairs that match or exceed the stability of Watson-Crick base-pairs. Thus, carbocyclic exo-amino nucleosides can be taken into consideration in the design of novel basepairs for the extension of the genetic alphabet, or for other applications in biotechnology.

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Section: Discussionsupporting

confidence: 90%

Section: Synthesis Of Carbocyclic Exo-amino Nucleosides and Building mentioning

confidence: 99%

Section: Pairing Properties Of Oligonucleotidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Incorporation into Oligodeoxynucleotides of Carbocyclic exo-Amino Nucleosides

Yaren¹,

Röthlisberger²,

Leumann³

2012

Synthesis

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“…Although many candidate unnatural base pairs have been reported (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), only a few are actually replicable by DNA polymerases (10,11,13,16). Moreover, it is clear that most applications will require that the unnatural base pair not only be replicated with high efficiency and fidelity but also, that replication be at least approximately independent of sequence context.…”

mentioning

confidence: 99%

Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet

Malyshev

Dhami²,

Quach³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

160

130

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The natural four-letter genetic alphabet, comprised of just two base pairs (dA-dT and dG-dC), is conserved throughout all life, and its expansion by the development of a third, unnatural base pair has emerged as a central goal of chemical and synthetic biology. We recently developed a class of candidate unnatural base pairs, exemplified by the pair formed between d5SICS and dNaM. Here, we examine the PCR amplification of DNA containing one or more d5SICS-dNaM pairs in a wide variety of sequence contexts. Under standard conditions, we show that this DNA may be amplified with high efficiency and greater than 99.9% fidelity. To more rigorously explore potential sequence effects, we used deep sequencing to characterize a library of templates containing the unnatural base pair as a function of amplification. We found that the unnatural base pair is efficiently replicated with high fidelity in virtually all sequence contexts. The results show that, for PCR and PCR-based applications, d5SICS-dNaM is functionally equivalent to a natural base pair, and when combined with dA-dT and dG-dC, it provides a fully functional six-letter genetic alphabet.expanded genetic alphabet | hydrophobic | artificial DNA | unnatural nucleotides | bioinformatics E xpansion of the genetic alphabet to include an unnatural base pair has emerged as a central goal of chemical and synthetic biology. Success would represent a remarkable integration of orthogonal synthetic components into a fundamental biological system and build the foundation for a semisynthetic organism with increased potential for information storage and retrieval (1). Moreover, the constituent unnatural nucleotides could be used to site-specifically label DNA or RNA with different functionalities of interest (2-4) and potentially revolutionize the already ubiquitous in vitro applications of nucleic acids, such as aptamer and DNA/RNAzyme selections (5, 6), PCR-based diagnostics (7, 8), and DNA-based nanomaterials and devices (9).Although many candidate unnatural base pairs have been reported (10-21), only a few are actually replicable by DNA polymerases (10,11,13,16). Moreover, it is clear that most applications will require that the unnatural base pair not only be replicated with high efficiency and fidelity but also, that replication be at least approximately independent of sequence context. Sequence dependencies would cause biased amplification and effectively preclude many uses of the unnatural base pair. No candidate unnatural base pair has been shown to be replicated without sequence bias, and thus, none can yet claim functional equivalence to a natural base pair.In general, the most promising unnatural base pair candidates currently available have been developed by pursuing one of two different strategies. The first strategy, pioneered in the work by Benner and coworkers (22), relies on the use of nucleotide analogs bearing nucleobases that pair through complementary hydrogen bonding (H-bonding) patterns that are orthogonal to those patterns of the natural pairs. Early ef...

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Nucleobases with Designed Patterns of Hydrogen Bonding

Fraser¹

2012

Advances in Heterocyclic Chemistry Volume 107

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A Parallel Screen for the Discovery of Novel DNA Base Pairs

Cited by 7 publications

References 30 publications

Synthesis and Incorporation into Oligodeoxynucleotides of Carbocyclic exo-Amino Nucleosides

Synthesis and Incorporation into Oligodeoxynucleotides of Carbocyclic exo-Amino Nucleosides

Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet

Nucleobases with Designed Patterns of Hydrogen Bonding

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