The use of the Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction for the
preparation of oligonucleotide conjugates is by now familiar. However, the selective
introduction of boronic acids into DNA and RNA sequences by CuAAC reactions has long
been considered impossible due to the incompatibility of the boronic acid moiety with
copper salts. Here we describe two new methods for the selective on-column functionalization
of oligonucleotides with boronic acids via two different CuAAC reactions. The first
one allows the introduction of a phenylboronic acid at the 5′-extremity of oligonucleotides,
while the selective intrastrand positioning of the modification can be achieved with
the second one. Both methods were applied to the DNA and RNA series (up to a 20-mer)
with good isolated yields and excellent purities. These results illustrate the potential
of the reported methods for selective incorporation of boronic acids into oligonucleotides.
Key words
CuAAc - boronic acid - oligonucleotide - bioconjugation - DNA - RNA
