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Science 12 March 1993:
Vol. 259. no. 5101, pp. 1564 - 1570
DOI: 10.1126/science.7681216
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Articles

Science, Vol 259, Issue 5101, 1564-1570
Copyright © 1993 by American Association for the Advancement of Science

articles

Phosphorodithioate DNA as a potential therapeutic drug

WS Marshall and MH Caruthers

Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.

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.


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J. Gen. Virol. 88, 981-990
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Newly Designed Six-Membered Azasugar Nucleotide-Containing Phosphorothioate Oligonucleotides as Potent Human Immunodeficiency Virus Type 1 Inhibitors.
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Single base extension (SBE) with proofreading polymerases and phosphorothioate primers: improved fidelity in single-substrate assays.
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Construction and selection of bead-bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries designed for rapid PCR-based sequencing.
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Suppression of Human Immunodeficiency Virus Type 1 Activity in Vitro by Oligonucleotides Which Form Intramolecular Tetrads.
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Present status and future prospects for HIV therapies.
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Science 260, 1286-1293
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