RNAs Containing Carbocyclic Ribonucleotides
Masaaki Akabane‐Nakata, Tyler Chickering, Joel M. Harp, Mark K. Schlegel, Shigeo Matsuda, Martin Egli, Muthiah Manoharan
Abstract
Toward the goal of evaluation of carbocyclic ribonucleoside-containing oligonucleotide therapeutics, we developed convenient, scalable syntheses of all four carbocyclic ribonucleotide phosphoramidites and the uridine solid-support building block. Crystallographic analysis confirmed configuration and stereochemistry of these building blocks. Duplexes with carbocyclic RNA (car-RNA) modifications in one strand were less thermodynamically stable than duplexes with unmodified RNA. However, circular dichroism spectroscopy indicated that global conformations of the duplexes containing car-RNAs were similar to those in the unmodified duplexes.