       Document 0022
 DOCN  M9620022
 TI    Ribozyme mimics as catalytic antisense reagents.
 DT    9602
 AU    Bashkin JK; Sampath U; Frolova E; Department of Chemistry, Washington
       University, St. Louis, MO; 63130-4899, USA.
 SO    Appl Biochem Biotechnol. 1995 Jul-Sep;54(1-3):43-56. Unique Identifier :
       AIDSLINE MED/96025581
 AB    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 HIV gag gene,
       using a ribozyme mimic. The reagent is composed of a terpyridylCu(II)
       complex for cleavage activity and an oligonucleotide for sequence
       specificity.
 DE    Animal  Antiviral Agents  Base Sequence  Drug Design  Gene Products,
       gag/*GENETICS/METABOLISM  Human  Hydrolysis  Molecular Sequence Data
       *RNA, Antisense  RNA, Catalytic/*METABOLISM  RNA, Messenger/ANTAGONISTS
       & INHIB  Support, Non-U.S. Gov't  JOURNAL ARTICLE  REVIEW  REVIEW,
       TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

