ja9740834_si_001.pdf (238.54 kB)
Postsynthetic Conjugation of Protected Oligonucleotides Containing 3‘-Alkylamines
journal contribution
posted on 1998-03-31, 00:00 authored by Dustin L. McMinn, Marc M. GreenbergThe expansion of a highly efficient, convergent method for
synthesizing 3‘-oligonucleotide conjugates
is described. 3‘-Oligonucleotide conjugates containing amide or
urea linkages between the oligonucleotide
portion and the conjugated species were obtained by reacting protected
oligonucleotides containing
3‘-alkylamines in aprotic organic solvents with carboxylic acid and
isocyanate substrates, respectively. The
protected oligonucleotides are obtained via standard automated
synthesis on a photolabile solid-phase synthesis
support. Excellent yields (83−100%) of bioconjugates were
obtained using carboxylic acids and aryl isocyanates
with as few as 5 molar equivalents of conjugation reagents relative to
protected oligonucleotide. More moderate
yields were obtained using alkyl isocyanates as substrates (70−88%).
In addition, this method has proven to
be useful for synthesizing complementary oligonucleotide−peptide
conjugates from a single oligonucleotide,
in which the polarity of the peptide with respect to the
oligonucleotide is determined by the bond-forming
process employed.