2′F-Arabinonucleic acids (2′F-ANA) — History, properties, and new frontiers

The development of arabinonucleosides and oligoarabinonucleotides is described, focusing especially on 2′-deoxy-2′-fluoroarabinonucleosides (araF-N) and -oligonucleotides (2'F-ANA). In addition to their chemical and enzymatic synthesis, we discuss various properties of 2′F-ANA: hydrolytic stability (to nucleases, acids, and bases), binding affinity to complementary strands, structure and conformation, and optimization of RNase H activity. We also discuss the use of 2′F-ANA in gene-silencing approaches (antisense, siRNA), and in the stabilization of higher-order structures (such as triplexes and quadruplexes) including aptamers. Finally, we examine several other oligonucleotide derivatives based on 2′F-ANA and look ahead to the future of 2′-fluoroarabinonucleosides and -oligonucleotides.