A double-headed nucleotide with two cytosines: DNA with condensed information and improved duplex stability

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Resumé

Double-headed nucleotide monomers are capable of condensing the genetic information of DNA. Herein, a double-headed nucleotide with two cytosine bases (CC) is constructed. The additional cytosine is connected through a methylene linker to the 2′-position of arabinocytidine. The nucleotide is incorporated into oligonucleotides and its effect on duplex stability is studied. For single incorporations, a thermal stabilization of 4.0 °C is found as compared to the unmodified duplex and it is shown that both nucleobases of CC participate in Watson-Crick base pairing. In combination with the previously published UT monomer, it is also shown that multiple incorporations are tolerated. For instance, a 16-mer sequence is targeted by a 13-mer oligonucleotide by using one CC and two UT monomers without compromising the overall duplex stability. Finally, the potential of double-headed nucleotides in triplex-forming oligonucleotides is studied, however, with the conclusion that the present design is not well-suited for this function.

SprogEngelsk
TidsskriftBioorganic and Medicinal Chemistry Letters
ISSN0960-894X
DOI
StatusAccepteret/In press - 1 jan. 2019

Bibliografisk note

Available online 5 January 2019

Fingeraftryk

Cytosine
Nucleotides
Oligonucleotides
Monomers
DNA
Base Pairing
Stabilization

Emneord

    Citer dette

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    title = "A double-headed nucleotide with two cytosines: DNA with condensed information and improved duplex stability",
    abstract = "Double-headed nucleotide monomers are capable of condensing the genetic information of DNA. Herein, a double-headed nucleotide with two cytosine bases (CC) is constructed. The additional cytosine is connected through a methylene linker to the 2′-position of arabinocytidine. The nucleotide is incorporated into oligonucleotides and its effect on duplex stability is studied. For single incorporations, a thermal stabilization of 4.0 °C is found as compared to the unmodified duplex and it is shown that both nucleobases of CC participate in Watson-Crick base pairing. In combination with the previously published UT monomer, it is also shown that multiple incorporations are tolerated. For instance, a 16-mer sequence is targeted by a 13-mer oligonucleotide by using one CC and two UT monomers without compromising the overall duplex stability. Finally, the potential of double-headed nucleotides in triplex-forming oligonucleotides is studied, however, with the conclusion that the present design is not well-suited for this function.",
    keywords = "Double-headed nucleotides, Duplex, Nucleic acids, Oligonucleotides, Triplex",
    author = "Kasper Beck and Charlotte Reslow-Jacobsen and Mick Hornum and Christian Henriksen and Poul Nielsen",
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    T2 - Bioorganic & Medicinal Chemistry Letters

    AU - Beck, Kasper

    AU - Reslow-Jacobsen, Charlotte

    AU - Hornum, Mick

    AU - Henriksen, Christian

    AU - Nielsen, Poul

    N1 - Available online 5 January 2019

    PY - 2019/1/1

    Y1 - 2019/1/1

    N2 - Double-headed nucleotide monomers are capable of condensing the genetic information of DNA. Herein, a double-headed nucleotide with two cytosine bases (CC) is constructed. The additional cytosine is connected through a methylene linker to the 2′-position of arabinocytidine. The nucleotide is incorporated into oligonucleotides and its effect on duplex stability is studied. For single incorporations, a thermal stabilization of 4.0 °C is found as compared to the unmodified duplex and it is shown that both nucleobases of CC participate in Watson-Crick base pairing. In combination with the previously published UT monomer, it is also shown that multiple incorporations are tolerated. For instance, a 16-mer sequence is targeted by a 13-mer oligonucleotide by using one CC and two UT monomers without compromising the overall duplex stability. Finally, the potential of double-headed nucleotides in triplex-forming oligonucleotides is studied, however, with the conclusion that the present design is not well-suited for this function.

    AB - Double-headed nucleotide monomers are capable of condensing the genetic information of DNA. Herein, a double-headed nucleotide with two cytosine bases (CC) is constructed. The additional cytosine is connected through a methylene linker to the 2′-position of arabinocytidine. The nucleotide is incorporated into oligonucleotides and its effect on duplex stability is studied. For single incorporations, a thermal stabilization of 4.0 °C is found as compared to the unmodified duplex and it is shown that both nucleobases of CC participate in Watson-Crick base pairing. In combination with the previously published UT monomer, it is also shown that multiple incorporations are tolerated. For instance, a 16-mer sequence is targeted by a 13-mer oligonucleotide by using one CC and two UT monomers without compromising the overall duplex stability. Finally, the potential of double-headed nucleotides in triplex-forming oligonucleotides is studied, however, with the conclusion that the present design is not well-suited for this function.

    KW - Double-headed nucleotides

    KW - Duplex

    KW - Nucleic acids

    KW - Oligonucleotides

    KW - Triplex

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    U2 - 10.1016/j.bmcl.2019.01.002

    DO - 10.1016/j.bmcl.2019.01.002

    M3 - Journal article

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    JF - Bioorganic & Medicinal Chemistry Letters

    SN - 0960-894X

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