Synthesis of Dihydroxyalkynyl and Dihydroxyalkyl Nucleotides as Building Blocks or Precursors for Introduction of Diol or Aldehyde Groups to DNA for Bioconjugations

0493205 - ÚOCHB 2019 RIV DE eng J - Journal Article
Krömer, Matouš - Bártová, Kateřina - Raindlová, Veronika - Hocek, Michal
Synthesis of Dihydroxyalkynyl and Dihydroxyalkyl Nucleotides as Building Blocks or Precursors for Introduction of Diol or Aldehyde Groups to DNA for Bioconjugations.
Chemistry - A European Journal. Roč. 24, č. 46 (2018), s. 11890-11894. ISSN 0947-6539. E-ISSN 1521-3765
R&D Projects: GA ČR GA15-08434S; GA MŠMT(CZ) EF16_019/0000729
Grant - others:AV ČR(CZ) AP1501
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:61388963
Keywords : aldehydes * bioconjugations * DNA * reactive groups * reductive amination
OECD category: Organic chemistry
Impact factor: 5.160, year: 2018

(3,4-Dihydroxybut-1-ynyl)uracil, -cytosine and -7-deazaadenine 2'-deoxyribonucleoside triphosphates (dNTPs) were prepared by direct aqueous Sonogashira cross-coupling of halogenated dNTPs with dihydroxybut-1-yne and converted to 3,4-dihydroxybutyl dNTPs through catalytic hydrogenation. Sodium periodate oxidative cleavage of dihydroxybutyl-dUTP gave the desired aliphatic aldehyde-linked dUTP, whereas the oxidative cleavage of the corresponding deazaadenine dNTP gave a cyclic aminal. All dihydroxyalkyl or -alkynyl dNTPs and the formylethyl-dUTP were good substrates for DNA polymerases and were used for synthesis of diol- or aldehyde-linked DNA. The aldehyde linked DNA was used for the labelling or bioconjugations through hydrazone formation or reductive aminations.
Permanent Link: http://hdl.handle.net/11104/0286612