Synthesis and Biophysical Characterization of RNAs Containing 2′-Fluorinated Northern Methanocarbacyclic Nucleotides
- 20 March 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in Organic Letters
- Vol. 21 (7) , 1963-1967
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.Keywords
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