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Cancer Res. 1994 Nov 15;54(22):5783-7.

Discovery of short, 3'-cholesterol-modified DNA duplexes with unique antitumor cell activity.

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  • 1Department of Pharmacology, School of Medicine, Yale University, Sterling Hall of Medicine, New Haven, Connecticut 06510.

Abstract

A new class of modified oligodeoxynucleotides with unique, selective cytotoxic properties has been discovered. Self-complementary, 3'-cholesterol-modified oligodeoxynucleotides caused morphology changes and death in certain cancer cell lines, whereas other cell lines were unaffected. Susceptible cells were killed in a dose-dependent manner at submicromolar concentrations. Optimum potency was exhibited by phosphodiester duplexes approximately 10 base pairs in length, and base composition was important only in the context of duplex stability. Phosphorothioate analogues were less potent. Although the molecular mechanism of action of these unique compounds is not yet known, they offer potential applications in cancer therapy and in studies of cell death. In addition, the path toward elucidation of the structure-based biological activity of these oligonucleotides should be especially instructive for researchers studying sequence-specific effects.

PMID:
7954399
[PubMed - indexed for MEDLINE]
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