Ribozyme mimics as catalytic antisense reagents

  • James K. Bashkin
  • Umashanker Sampath
  • Elena Frolova
Part I. RNA Science and RNA Technology

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.

Index Entries

Hydrolytic cleavage of RNA sequence-directed by ribozyme mimic copper(II) terpyridine-catalyzed controlling gene expression gene-specific drugs for antisense method of chemoselective reagents for 

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Copyright information

© Humana Press Inc. 1995

Authors and Affiliations

  • James K. Bashkin
    • 1
  • Umashanker Sampath
    • 1
  • Elena Frolova
    • 1
  1. 1.Department of ChemistryWashington UniversitySt. Louis

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