A new route to 2′-O-alkyl-2-thiouridine derivatives via 4-o-protection of the uracil base and hybridization properties of oligonucleotides incorporating these modified nucleoside derivatives

Oligonucleotides containing 2-thiouridine (s(2)U) in place of uridine form stable RNA duplexes with complementary RNAs. Particularly, this modified nucleoside has proved to recognize highly selectively adenosine, the genuine partner, without formation of a mismatched base pair with the guanosine counterpart. In this paper, we describe new methods for the synthesis of 2-thiouridine and various 2'-O-alkyl-2-thiouridine derivatives. Oligoribonucleotides having these modified nucleoside derivatives were synthesized, and their hybridization and structural properties were studied in detail by the H-1 NMR analysis of these modified nucleosides and T-m experiments of RNA duplexes with their complementary RNA strands.