A double-headed nucleotide with two cytosines

DNA with condensed information and improved duplex stability

Kasper Beck, Charlotte Reslow-Jacobsen, Mick Hornum, Christian Henriksen, Poul Nielsen*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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.

OriginalsprogEngelsk
TidsskriftBioorganic and Medicinal Chemistry Letters
Vol/bind29
Udgave nummer5
Sider (fra-til)740-743
ISSN0960-894X
DOI
StatusUdgivet - 1. mar. 2019

Fingeraftryk

Cytosine
Nucleotides
Oligonucleotides
Monomers
DNA
Base Pairing
Stabilization

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.",
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author = "Kasper Beck and Charlotte Reslow-Jacobsen and Mick Hornum and Christian Henriksen and Poul Nielsen",
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A double-headed nucleotide with two cytosines : DNA with condensed information and improved duplex stability. / Beck, Kasper; Reslow-Jacobsen, Charlotte; Hornum, Mick; Henriksen, Christian; Nielsen, Poul.

I: Bioorganic and Medicinal Chemistry Letters, Bind 29, Nr. 5, 01.03.2019, s. 740-743.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A double-headed nucleotide with two cytosines

T2 - DNA with condensed information and improved duplex stability

AU - Beck, Kasper

AU - Reslow-Jacobsen, Charlotte

AU - Hornum, Mick

AU - Henriksen, Christian

AU - Nielsen, Poul

N1 - Available online 5 January 2019

PY - 2019/3/1

Y1 - 2019/3/1

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.

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KW - Duplex

KW - Nucleic acids

KW - Oligonucleotides

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