Chemical Synthesis of Modified Oligonucleotides Containing 5'-Amino-5'-Deoxy-5'-Hydroxymethylthymidine Residues.

Introduction of cationic modifications into an oligonucleotide can increase its nuclease resistance and duplex- or triplex-forming abilities. In a recent study, we found that the nuclease resistance and RNA binding selectivity of an oligonucleotide containing a 5'-(R)-amino-5'-deoxy-5'-(R)-hydroxymethylthymidine residue were greater than those of the unmodified oligonucleotide. In this article, we describe the synthesis of 5'-amino-5'-deoxy-5'-hydroxymethylthymidine via dihydroxylation of the 5'-alkene derivative using either of two commercial AD (asymmetric dehydroxylation) mixes or via epoxidation and ring opening.

Chemical synthesis and properties of modified oligonucleotides containing 5'-amino-5'-deoxy-5'-hydroxymethylthymidine residues.

In this study, we designed 5'-amino-5'-deoxy-5'-hydroxymethylthymidine as a new oligonucleotide modification with an amino group directly attached to the 5'-carbon atom. We successfully synthesized two isomers of 5'-amino-5'-deoxy-5'-hydroxymethylthymidine via dihydroxylation of the 5'-vinyl group incorporated into 5'-deoxy-5'-C-methenylthymidine derivative. Moreover, it was found that the nuclease resistance, binding selectivity to single-stranded RNA, and triplex-forming ability of an oligonucleotide containing T residues of the new compound were higher than those of the unmodified oligonucleotide.