A Postsynthetic Strategy for Oligonucleotides Containing 2-Fluoro-adenine and Isoguanine Nucleobases
Mimouna Madaoui1, Jayanta Kundu1, Dhrubajyoti Datta1
1Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.
Abstract:
We describe a strategy for the synthesis of DNA, RNA and 2'-O-methyl (2'-O-Me) oligonucleotides containing 2-fluoro-adenine (AF) and isoguanine (iG) nucleobases. To the best of our knowledge, this is the first nonenzymatic route for the synthesis of oligonucleotides containing 2-fluoro-adenine. We also describe the hydrolytic strategy for the conversion of 2-fluoro-adenine into isoguanine. Unlike 2,6-diaminopurine, 2-fluoro-adenine and isoguanine modifications are thermally destabilizing in the context of DNA, RNA, and 2'-O-methyl oligonucleotide duplexes.
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