Nucleosides and nucleotides. 121. Synthesis of oligonucleotides carrying linker groups at the 1'-position of sugar residues

Ono, Akira; Dan, Akihito; Matsuda, Akira

doi:10.1021/bc00024a012

Cited by 40 publications

(38 citation statements)

References 22 publications

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“…On the contrary, polyamines are known to have high binding affinity for DNA and to increase duplex (17) and triplex stabilities (18). Thus, we synthesized oligonucleotides carrying various polyamines at the nucleobases (19–23) or at the sugar rings (24–26). Some of them stabilized duplexes and triplexes and enhanced nuclease resistance.…”

Section: Introductionmentioning

confidence: 99%

Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N-aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules

Juan¹,

Kondo²,

Kurihara³

et al. 2007

Nucleic Acids Research

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Oligonucleotides containing 5-(N-aminohexyl)carbamoyl-modified uracils have promising features for applications as antigene and antisense therapies. Relative to unmodified DNA, oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2′-deoxyuridine (NU) or 5-(N-aminohexyl)carbamoyl-2′-O-methyluridine (NUm), respectively exhibit increased binding affinity for DNA and RNA, and enhanced nuclease resistance. To understand the structural implications of NU and NUm substitutions, we have determined the X-ray crystal structures of DNA:DNA duplexes containing either NU or NUm and of DNA:RNA hybrid duplexes containing NUm. The aminohexyl chains are fixed in the major groove through hydrogen bonds between the carbamoyl amino groups and the uracil O4 atoms. The terminal ammonium cations on these chains could interact with the phosphate oxygen anions of the residues in the target strands. These interactions partly account for the increased target binding affinity and nuclease resistance. In contrast to NU, NUm decreases DNA binding affinity. This could be explained by the drastic changes in sugar puckering and in the minor groove widths and hydration structures seen in the NUm containing DNA:DNA duplex structure. The conformation of NUm, however, is compatible with the preferred conformation in DNA:RNA hybrid duplexes. Furthermore, the ability of NUm to render the duplexes with altered minor grooves may increase nuclease resistance and elicit RNase H activity.

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Section: Introductionmentioning

confidence: 99%

Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N-aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules

Juan¹,

Kondo²,

Kurihara³

et al. 2007

Nucleic Acids Research

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“…To incorporate an AQ sensitizer into the DNA backbone, ODN 1A C H T U N G T R E N N U N G (AQ 1 ) was prepared by coupling AQ succinimidyl ester [27] with ODN (N), which possessed an amino linker in the middle of sequential bases. [28] In this study, we used a partial sequence of the human p53 gene corresponding to codons 280-285 of exon 8 and targeted the m C at codon 282.…”

Section: Resultsmentioning

confidence: 99%

“…Anthraquinone 2-carboxylic acid N-hydroxysuccinimidyl ester (AQ-NHS) and 2-(3-bromopropionamido)anthraquinone were prepared following reported methods. [27,37] The reagents for the DNA synthesizer were purchased from Glen Research. Oligodeoxynucleotides (ODNs) containing an amino linker were synthesized on an Applied Biosystems Model 3400 DNA/RNA synthesizer with BD Uni-Link AminoModifier (BD Biosicences Clontech).…”

Section: Methodsmentioning

confidence: 99%

Anthraquinone‐Sensitized Photooxidation of 5‐Methylcytosine in DNA Leading to Piperidine‐Induced Efficient Strand Cleavage

Yamada

Kitauchi

Tanabe

et al. 2011

Chemistry A European J

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One-electron photooxidations of 5-methyl-2'-deoxycytidine (d(m)C) and 5-trideuteriomethyl-2'-deoxycytidine ([D(3)]d(m)C) by sensitization with anthraquinone (AQ) derivatives were investigated. Photoirradiation of an aerated aqueous solution containing d(m)C and anthraquinone 2-sulfonate (AQS) afforded 5-formyl-2'-deoxycytidine (d(f)C) and 5-hydroxymethyl-2'-deoxycytidine (d(hm)C) in good yield through an initial one-electron oxidation process. The deuterium isotope effect on the AQS-sensitized photooxidation of d(m)C suggests that the rate-determining step in the photosensitized oxidation of d(m)C involves internal transfer of the C5-hydrogen atom of a d(m)C-tetroxide intermediate to produce d(f)C and d(hm)C. In the case of a 5-methylcytosine ((m)C)-containing duplex DNA with an AQ chromophore that is incorporated into the backbone of the DNA strand so as to be immobilized at a specific position, (m)C underwent efficient direct one-electron oxidation by the photoexcited AQ, which resulted in an exclusive DNA strand cleavage at the target (m)C site upon hot piperidine treatment. In accordance with the suppression of the strand cleavage at 5-trideuterio-methylcytosine observed in a similar AQ photosensitization, it is suggested that deprotonation at the C5-methyl group of an intermediate (m)C radical cation may occur as a key elementary reaction in the photooxidative strand cleavage at the (m)C site. Incorporation of an AQ sensitizer into the interior of a strand of the duplex enhanced the one-electron photooxidation of (m)C, presumably because of an increased intersystem crossing efficiency that may lead to efficient piperidine-induced strand cleavage at an (m)C site in a DNA duplex.

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“…Numerous past reports have characterized the strong tendency for anthraquinone derivatives to intercalate into duplex DNA (see for example [16][17][18][19][20][21][22][23][24][25][26][27] and therefore a similar interaction was expected for the duplexes formed by the dimethylanthraquinone-oligodeoxynucleotide conjugate and its complementary target. This non-covalent binding was characterized by an increase in the thermal melting temperature (T m ) of duplex DNA in the presence of the quinone (Table 1).…”

Section: Anthraquinone Stabilizes Duplex Hybridizationmentioning

confidence: 99%

“…Numerous bis(aminoalkyl) anthraquinones have also been prepared as anticancer agents based on their strength as intercalators (17)(18)(19) and this binding property has since been used to promote platinum-DNA reaction through construction of anthraquinone-cisplatin conjugates (20). Anthraquinone derivatives have similarly been coupled to antisense and antigene reagents in order to strengthen their association with target DNA, as well as to enhance their cellular uptake and decrease their sensitivity to nucleases (21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Site-specific and photo-induced alkylation of DNA by a dimethylanthraquinone-oligodeoxynucleotide conjugate

Kang

Rokita

1996

Nucleic Acids Research

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A dialkyl-substituted anthraquinone derivative was synthesized and ligated to a sequence-directing oligodeoxynucleotide to examine its efficiency and specificity for cross-linking to complementary sequences of DNA. The anthraquinone appendage stabilized spontaneous hybridization of the target and probe sequences through non-covalent interactions, as indicated by thermal denaturation studies. Covalent modification of the target was induced by exposure to near UV light (λ > 335 nm) to generate cross-linked duplexes in yields as great as 45%. Reaction was dependent on the first unpaired nucleotide extended beyond the duplex formed by association of the target and probe. A specificity of C > T > A ≈ G was determined for modification at this position. The overall site and nucleotide selectivity seems to originate from the chemical requirements of cross-linking and does not likely reflect the dominant solution structure of the complex prior to irradiation.

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Nucleosides and nucleotides. 121. Synthesis of oligonucleotides carrying linker groups at the 1'-position of sugar residues

Cited by 40 publications

References 22 publications

Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N-aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules

Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N-aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules

Anthraquinone‐Sensitized Photooxidation of 5‐Methylcytosine in DNA Leading to Piperidine‐Induced Efficient Strand Cleavage

Site-specific and photo-induced alkylation of DNA by a dimethylanthraquinone-oligodeoxynucleotide conjugate

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