Phosphorodithioate DNA as a potential therapeutic drug

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Science  12 Mar 1993:
Vol. 259, Issue 5101, pp. 1564-1570
DOI: 10.1126/science.7681216


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.