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Ribozyme mimics as catalytic antisense reagents

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Abstract

Viral and fungal infections and some cancers may be described as diseases that are characterized by the expression of certain unwanted proteins. They could be termed induced genetic disorders, with induction provided by mutation or infection. A comprehensive method to inactivate injurious genes based on their nucleic acid sequences has the potential to provide effective antiviral and anticancer agents with greatly reduced side effects. We describe a chemical approach to such gene-specific pharmaceutical agents. Our initial efforts have been to develop new chemical reagents that can carry out catalytic destruction of specific mRNA sequences. We chose hydrolysis as a chemical means of destruction, because hydrolysis is compatible with living cells. Our sequence-specific catalytic RNA hydrolysis reagents may be described as functional ribozyme mimics. Reactivity is provided by small-molecule catalysts, such as metal complexes. Specificity is provided by oligonucleotide probes. Here we report initial results on the sequence-specific, hydrolytic cleavage of mRNA from the HIVgag gene, using a ribozyme mimic. The reagent is composed of a terpyridylCu(II) complex for cleavage activity and an oligonucleotide for sequence specificity.

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Authors and Affiliations

  1. Department of Chemistry, Washington University, 1 Brookings Drive, Box 1134, 63130-4899, St. Louis, MO

    James K. Bashkin, Umashanker Sampath & Elena Frolova

Authors
  1. James K. Bashkin
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  2. Umashanker Sampath
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  3. Elena Frolova
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Bashkin, J.K., Sampath, U. & Frolova, E. Ribozyme mimics as catalytic antisense reagents. Appl Biochem Biotechnol 54, 43–56 (1995). https://doi.org/10.1007/BF02787910

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