Properties of 5- and/or 2-modified 2′-O-cyanoethyl uridine residue: 2′-O-cyanoethyl-5-propynyl-2-thiouridine as an efficient duplex stabilizing component

Abstract

We systematically synthesized eight types of 5- and/or 2-modified uridine derivatives and evaluated their effect on duplex stability. The incorporation of 2′-O-cyanoethyl-2-thio-5-propynyluridine (p⁵s²U_OCE) into RNA was significantly effective for stabilization of RNA/RNA (+8.5 °C) and DNA/RNA (+10.4 °C) duplexes. These striking effects were maintained in oligonucleotides with different sequences or multiple incorporations. In addition, p⁵s²U_OCE increased selectivity toward the correct AU Watson–Crick base pair over the most stable mismatched base pair in both RNA/RNA and DNA/RNA duplexes. Hence, p⁵s²U_OCE could be useful for various applications of modified oligonucleotides that need high duplex stability and base pairing selectivity.