Phosphorodithioate DNA as a potential therapeutic drug.
This article summarizes methods for the synthesis of phosphorodithioate-linked deoxyoligonucleotides and details an analysis of one of the distinctive properties of phosphorodithioate DNA oligomers, their ability to strongly inhibit human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT). Mechanistic studies indicate that oligomers of this type interfere with enzyme function by binding tightly to the active site for primer-template, which results in low or subnanomolar inhibitory constants. Although many of these studies have used deoxyoligocytidine analogs, a rationally designed approach has led to the discovery of a very active phosphorodithioate deoxyoligonucleotide inhibitor. This type of inhibitor, which binds strongly to the primer-template active site of HIV-1 RT, provides another type of potential therapeutic agent against HIV-1.
Marshall
W S
WS
Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.
Caruthers
M H
MH
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001483:Base Sequence; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D063086:Organothiophosphates / Q000138:chemical synthesis* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides; D063086:Organothiophosphates; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase