Flexible Alkyne-Linked Thymidine Phosphoramidites and Triphosphates for Chemical or Polymerase Synthesis and Fast Postsynthetic DNA Functionalization through Copper-Catalyzed Alkyne-Azide 1,3-Dipolar Cycloaddition.

Abstract

Two alternative flexible alkyne-linked thymine nucleosides (propargyl-diethylene glycol- or undecyn-linked 5-hydroxymethyluracil derivatives), as well as their phosphoramidites and triphosphates, were designed and synthesized. The nucleoside 3'- O-phosphoramidites were successfully incorporated into oligonucleotides on a solid support, whereas the nucleoside triphosphates served as good substrates for polymerase synthesis of modified DNA, which underwent fast and efficient copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reactions.