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Feb 26, 2001
 |  BioCentury  |  Tools & Techniques

Making nucleoside analogs safer

While several nucleoside analogs have made it to market, a number have failed in late stage trials due to severe toxicity. But work published in last week's Proceedings of the National Academy of Sciences may make it easier to design nucleoside analogs with better safety profiles.

Nucleoside analogs are designed to be similar to deoxyribonucleotides, the building blocks of DNA. They are used to treat viral infections including HIV and hepatitis because they bind to the viral reverse transcriptase and halt viral proliferation.

Antiviral nucleoside analogs also are designed to have low affinity for nuclear DNA polymerase, which allows them to inhibit viral proliferation without inhibiting normal mitosis. According to the PNAS report, researchers with the Dunn-Human Nutrition Unit (Cambridge, U.K.) and the University of Calabria (Cosenza, Italy) have discovered a protein that appears to function as a mitochondrial deoxynucleotide carrier (DNC), which shuttles deoxynucleotides into the organelle for use in mitochondrial DNA synthesis.

Analysis of this transport molecule may improve the design of nucleoside analogs because...

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