Enzymatic synthesis of biphenyl-DNA oligonucleotides

Pascal Röthlisberger (1) , Fabienne Levi-Acobas (1) , Christian Leumann (2) , Marcel Hollenstein (1)

1 Chimie bioorganique des acides nucléiques - Bioorganic chemistry of nucleic acids
2 University of Bern

The incorporation of nucleotides equipped with C-glycosidic aromatic nucleobases into DNA and RNA is an alluring strategy for a number of practical applications including fluorescent labelling of oligonucleotides, expansion of the genetic alphabet for the generation of aptamers and semi-synthetic organisms, or the modulation of excess electron transfer within DNA. However, the generation of C-nucleoside containing oligonucleotides relies mainly on solid-phase synthesis which is quite labor intensive and restricted to short sequences. Here, we explore the possibility of constructing biphenyl-modified DNA sequences using enzymatic synthesis. The presence of multiple biphenyl-units or biphenyl residues modified with electron donors and acceptors permits the incorporation of a single dBphMP nucleotide. Moreover, templates with multiple abasic sites enable the incorporation of up to two dBphMP nucleotides, while TdT-mediated tailing reactions produce single-stranded DNA oligonucleotides with four biphenyl residues appended at the 3'-end.

Keywords: Biaryls; DNA polymerases; Hydrophobic bases; Modified nucleic acids; Nucleoside triphosphates

Domains: Chemical Sciences; Chemical Sciences; Organic chemistry

Pascal Röthlisberger, Fabienne Levi-Acobas, Christian Leumann, Marcel Hollenstein. Enzymatic synthesis of biphenyl-DNA oligonucleotides. Bioorganic and Medicinal Chemistry, 2020, 28 (11), pp.115487. ⟨10.1016/j.bmc.2020.115487⟩. ⟨pasteur-02625707⟩