Highly Efficient and Selective Cross-Linking to Cytidine Based on a New Strategy for Auto-Activation within a Duplex

Nagatsugi, Fumi; Kawasaki, Takeshi; Usui, Daisaku; Maëda, Minoru; Sasaki, Shigeki

doi:10.1021/ja990356e

Cited by 80 publications

(48 citation statements)

References 22 publications

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“…This compound exhibited efficient and selective cross-linking to cytosine bases (19–25). The close proximity of the vinyl group to the cytosine base in the hybridized complex contributed to the high reactivity of 1 (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

4-vinyl-substituted pyrimidine nucleosides exhibit the efficient and selective formation of interstrand cross-links with RNA and duplex DNA

Nishimoto

Jitsuzaki

Onizuka

et al. 2013

Nucleic Acids Research

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The formation of interstrand cross-links in nucleic acids can have a strong impact on biological function of nucleic acids; therefore, many cross-linking agents have been developed for biological applications. Despite numerous studies, there remains a need for cross-linking agents that exhibit both efficiency and selectivity. In this study, a 4-vinyl-substituted analog of thymidine (T-vinyl derivative) was designed as a new cross-linking agent, in which the vinyl group is oriented towards the Watson–Crick face to react with the amino group of an adenine base. The interstrand cross-link formed rapidly and selectively with a uridine on the RNA substrate at the site opposite to the T-vinyl derivative. A detailed analysis of cross-link formation while varying the flanking bases of the RNA substrates indicated that interstrand cross-link formation is preferential for the adenine base on the 5′-side of the opposing uridine. In the absence of a 5′-adenine, a uridine at the opposite position underwent cross-linking. The oligodeoxynucleotides probe incorporating the T-vinyl derivative efficiently formed interstrand cross-links in parallel-type triplex DNA with high selectivity for dA in the homopurine strand. The efficiency and selectivity of the T-vinyl derivative illustrate its potential use as a unique tool in biological and materials research.

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Section: Introductionmentioning

confidence: 99%

4-vinyl-substituted pyrimidine nucleosides exhibit the efficient and selective formation of interstrand cross-links with RNA and duplex DNA

Nishimoto

Jitsuzaki

Onizuka

et al. 2013

Nucleic Acids Research

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“…In these cases, the conformation and surface properties of nucleic acids likely contribute to the observed rate enhancements of reaction (18)(19)(20)(21)(22)(23)(24)(25). Probably the best studied example of this type of DNA-promoted process involves nucleobase reaction with cyclopropylpyrroloindole derivatives such as those found in natural products CC-1065 and the duocarmycins as well as a related synthetic analog bizelsin, currently undergoing clinical investigation (26)(27)(28)(29).…”

mentioning

confidence: 99%

A general strategy for target-promoted alkylation in biological systems

Zhou

Rokita²

2003

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

115

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“…The vinyl group of 1 was protected with methanethiol, and transformed to the amidite precursor (7) for incorporation into the oligodeoxynucleotides. The methylsulfide group of the ODN (8) was oxidized to the sulfoxide group, and then treated under alkaline conditions to generate a vinyl group (9). Addition of a variety of thiol compounds such as thiophenol to the vinyl group produces stable precursors (10).…”

Section: Design and Synthesis Of The Reactive Nucleoside Analogmentioning

confidence: 99%

Molecular Design for Specific Recognition and Reaction in Genome-Targeting Chemistry

Sasaki¹,

Nagatsugi²

2005

Frontiers in Organic Chemistry

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Molecules that can target DNA or RNA with high efficiency and specificity are of great interest because of potential applications to modulation of gene expression at a specific site. Our approach in genome-targeting chemistry has been focused on development of reactive molecules with high base-as well as sequence selectivity. This paper summarizes our contributions in this field. At first, a general concept of reactive molecules in genome-targeting chemistry is introduced. In the following section, molecular design to achieve specific and efficient reactions in the living system is described. Two new reactive molecules, 2-amino-6-vinylpurine derivative as an efficient cross-linking agent, and the Snitroso-6-thioguanosine as a selective S to N nitoroso group transfer agent are summarized. These two molecules demonstrate successful examples of reactive agents that are activated only in the complementary hybrids. In the third section, new nucleoside analogs to expand recognition codes of triplex formation are discussed. We have recently developed non-natural nucleoside analogs (W-shaped nucleoside analog: WNA) having a heterocyclic ring as a recognition unit and an aromatic ring as a stacking part on the bicyclo[3.3.0]octane skeleton. It has been shown that the two analogs, WNA-T with a thymine and WNA-C with a cytosine, exhibit stable formation of non-natural triplexes containing a TA and a CG interrupting site with high stability, respectively. These new genome-targeting molecules will be applied to artificial modulation of gene expression in vitro as well as in vivo.

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Highly Efficient and Selective Cross-Linking to Cytidine Based on a New Strategy for Auto-Activation within a Duplex

Cited by 80 publications

References 22 publications

4-vinyl-substituted pyrimidine nucleosides exhibit the efficient and selective formation of interstrand cross-links with RNA and duplex DNA

4-vinyl-substituted pyrimidine nucleosides exhibit the efficient and selective formation of interstrand cross-links with RNA and duplex DNA

A general strategy for target-promoted alkylation in biological systems

Molecular Design for Specific Recognition and Reaction in Genome-Targeting Chemistry

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