Document 0449
 DOCN  M9440449
 TI    Effect of a thiobenzimidazolone derivative on DNA strand transfer
       catalyzed by HIV-1 reverse transcriptase.
 DT    9404
 AU    Gopalakrishnan V; Benkovic S; Department of Chemistry, Pennsylvania
       State University,; University Park 16802.
 SO    J Biol Chem. 1994 Feb 11;269(6):4110-5. Unique Identifier : AIDSLINE
       MED/94140828
 AB    Thiobenzimidazolone (TIBO) derivatives are known inhibitors of the DNA
       polymerase activity of human immunodeficiency virus type 1 (HIV-1)
       reverse transcriptase (RT). The effect of a TIBO derivative
       ((+)-S-4,5,6,7-tetrahydro-9-chloro-5-
       methyl-6-(3-methyl-2-butenyl)-imidazol[4,5,1-jk]1,4-benzodiazapin- e
       -2-thione ) on the DNA strand transfer reaction catalyzed by HIV-1 RT
       (which is a function of both the DNA polymerase and RNase H activities)
       was investigated by delineating the effect of the drug on the
       constitutive DNA polymerase and RNase H activities) was investigated by
       delineating the effect of the drug on the constitutive DNA polymerase
       and RNase H activities. Single nucleotide incorporation on
       template-primer 1 was used to study the DNA polymerase activity of HIV-1
       RT while template-primer 2 was used to study the effect of TIBO on the
       RNase H activity (polymerase independent). The drug was found to
       decrease the amplitude of the presteady-state burst when preequilibrated
       with the enzyme-substrate complex besides decreasing the steady-state
       rate of single nucleotide incorporations. In the absence of
       preincubation, TIBO did not affect the burst amplitude but decreased the
       steady-state rate after the pre-transient phase. This suggested that
       binding of TIBO to RT was affected by the presence of template-primer
       and required dissociation of the enzyme from the template-primer for
       effective binding. The polymerase-independent RNase H activity was
       activated in the presence of TIBO. The effect of TIBO on the overall
       process of DNA strand transfer is a balance between its inhibition of
       the polymerase activity and its activation of the RNase H activity.
 DE    Antiviral Agents/PHARMACOLOGY  Base Sequence
       Benzodiazepines/*PHARMACOLOGY  DNA/*METABOLISM  DNA Primers/CHEMISTRY
       HIV-1/ENZYMOLOGY  Imidazoles/*PHARMACOLOGY  Molecular Sequence Data
       Reverse Transcriptase/*ANTAGONISTS & INHIB  Ribonuclease H, Calf
       Thymus/METABOLISM  Support, U.S. Gov't, P.H.S.  Templates  JOURNAL
       ARTICLE

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