Deoxyribonucleoside 2'- or 3'-Mixed Disulfides: Prodrugs To Target Ribonucleotide Reductase and/or To Inhibit HIV Reverse Transcription

摘要

Herein, we report the design, synthesis, and biological effects of nucleosides bearing a disulfide function on the sugar ring as prodrugs of potentially active mercapto-nucleotides that can target ribonucleotide reductase or reverse transcriptase. We show that cytidine derivatives efficiently reduce dNTP pools in human CEM/SS cells and that 3'-deoxythmidin-3'-yl methyl disulfide is able to interfere with both cellular dNTP synthesis and HIV reverse transcription.