Synthesis and Biophysical Characterization of RNAs Containing 2'-Fluorinated Northern Methanocarbacyclic Nucleotides.

ABSTRACT

2'-Fluorinated Northern methanocarbacyclic (2'-F-NMC) nucleosides and phosphoramidites, based on a bicyclo[3.1.0]hexane scaffold bearing all four natural nucleobases (U, C, A, and G), were synthesized to enable exploration of this novel nucleotide modification related to the clinically validated 2'-deoxy-2'-fluororibonucleotides (2'-F-RNA). Biophysical properties of the 2'-F-NMC-containing oligonucleotides were evaluated. A duplex of 2'-F-NMC-modified oligonucleotide with RNA exhibited thermal stability similar to that of the parent RNA duplex, 2'-F-NMC-modified oligonucleotides had higher stability against 5'- and 3'-exonucleolytic degradation than the corresponding oligonucleotides modified with 2'-F-RNA, and 2'-F-NMC-modified oligonucleotides exhibited higher lipophilicity than the corresponding RNA oligonucleotides as well as those modified with 2'-F-RNA.