Get access

Synthesis of Aldehyde-Linked Nucleotides and DNA and Their Bioconjugations with Lysine and Peptides through Reductive Amination

Authors

  • Veronika Raindlová,

    1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, 16610 Prague 6 (Czech Republic), Fax: (+420) 220-183-559 http://www.uochb.cas.cz/hocekgroup
    Search for more papers by this author
  • Dr. Radek Pohl,

    1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, 16610 Prague 6 (Czech Republic), Fax: (+420) 220-183-559 http://www.uochb.cas.cz/hocekgroup
    Search for more papers by this author
  • Prof. Dr. Michal Hocek

    Corresponding author
    1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, 16610 Prague 6 (Czech Republic), Fax: (+420) 220-183-559 http://www.uochb.cas.cz/hocekgroup
    2. Department of Organic and Nuclear Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2 (Czech Republic)
    • Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2, 16610 Prague 6 (Czech Republic), Fax: (+420) 220-183-559 http://www.uochb.cas.cz/hocekgroup
    Search for more papers by this author

Abstract

5-(5-Formylthienyl)-, 5-(4-formylphenyl)- and 5-(2-fluoro-5-formylphenyl)cytosine 2′-deoxyribonucleoside mono- (dCRMP) and triphosphates (dCRTP) were prepared by aqueous Suzuki–Miyaura cross-coupling of 5-iodocytosine nucleotides with the corresponding formylarylboronic acids. The dCRTPs were excellent substrates for DNA polymerases and were incorporated into DNA by primer extension or PCR. Reductive aminations of the model dCRMPs with lysine or lysine-containing tripeptide were studied and optimized. In aqueous phosphate buffer (pH 6.7) the yields of the reductive aminations with tripeptide III were up to 25 %. Bioconjugation of an aldehyde-containing DNA with a lysine-containing tripeptide was achieved through reductive amination in yields of up to 90 % in aqueous phosphate buffer.

Get access to the full text of this article

Ancillary