Synthesis of activated 3′-amino-3′-deoxy-2-thio-thymidine, a superior substrate for the nonenzymatic copying of nucleic acid templates

Abstract

We present a scalable synthesis of 3'-amino-3'-deoxy-2-thio-thymidine-5'-phosphoro-2-methylimidazolide, an activated monomer that can copy adenosine residues in nucleic acid templates rapidly without a polymerase. The sulfur atom substitution enhances the rate of template copying by 5-fold compared with the 3'-amino-3'-deoxy-T monomer, while the 3'-amino monomers exhibit a 2- to 3'-fold enhancement compared with their ribonucleotide counterparts.