A Chemical Approach to Introduce 2,6-Diaminopurine and 2-Aminoadenine Conjugates into Oligonucleotides without Need
Mimouna Madaoui1, Dhrubajyoti Datta1, Kelly Wassarman1
1Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.
Abstract:
We report a simple, postsynthetic strategy for synthesis of oligonucleotides containing 2,6-diaminopurine nucleotides and 2-aminoadenine conjugates using 2-fluoro-6-amino-adenosine. The strategy allows introduction of 2,6-diaminopurine and other 2-amino group-containing ligands. The strongly electronegative 2-fluoro deactivates 6-NH2 obviating the need for any protecting group on adenine, and simple aromatic nucleophilic substitution of fluorine makes reaction with aqueous NH3 or R-NH2 feasible at the 2-position.
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