       Document 0789
 DOCN  M9550789
 TI    Peyssonols A and B, two novel inhibitors of the reverse transcriptases
       of human immunodeficiency virus types 1 and 2.
 DT    9505
 AU    Loya S; Bakhanashvili M; Kashman Y; Hizi A; Department of Cell Biology
       and Histology, Sackler School of; Medicine, Tel Aviv, Israel.
 SO    Arch Biochem Biophys. 1995 Feb 1;316(2):789-96. Unique Identifier :
       AIDSLINE MED/95168866
 AB    Two new sesquiterpene hydroquinones, peyssonol A and peyssonol B, of the
       Red Sea algae Peyssonelia sp., have been shown to be potent inhibitors
       of the RNA-directed DNA synthesis of the reverse transcriptases (RTs) of
       human immunodeficiency virus (HIV)-1 and HIV-2. The DNA-dependent DNA
       polymerase activity is inhibited to a lesser extent, whereas the RNase H
       activity is unaffected. The inhibition of the DNA polymerase activities
       is independent of the nature of the template primers used. Peyssonol A
       probably binds the RT at a site distinct from those occupied by the
       substrates of the RNA-directed DNA synthesis, since the mode of
       inhibition is noncompetitive with respect to both dNTP's and template
       primer. This is partially true for peyssonol B, which is noncompetitive
       with respect to only dNTP, but is competitive with respect to the
       template primer. We have speculated that, since peyssonol B and the
       template primer bear no apparent structural resemblance, the competitive
       pattern of inhibition can be explained by an indirect steric hindrance
       or by the overlap of the inhibitor and the substrate distinct binding
       sites of the enzyme. Alternatively, the binding of the inhibitor to a
       distinct site induces conformational changes that distort the binding of
       the template primer. Furthermore, we have shown that both peyssonol A
       and peyssonol B interfere with the direct binding of the RT to the
       template primer, offering an explanation for the mechanism of the enzyme
       inhibition. The insensitivity of DNA polymerase beta and the poor
       response of DNA polymerase alpha to peyssonol A make this inhibitor more
       attractive for the future development of a potent anti-HIV RT drug.
 DE    Algae/CHEMISTRY  Comparative Study  Dose-Response Relationship, Drug
       DNA Polymerases/DRUG EFFECTS  DNA Primers/METABOLISM  Escherichia
       coli/GENETICS  Eukaryotic Cells/ENZYMOLOGY  Hydroquinones/*PHARMACOLOGY
       Protein Binding  Recombinant Proteins/ANTAGONISTS & INHIB/BIOSYNTHESIS
       Reverse Transcriptase/*ANTAGONISTS & INHIB/BIOSYNTHESIS/GENETICS/
       METABOLISM  Sesquiterpenes/*PHARMACOLOGY  Support, U.S. Gov't, P.H.S.
       JOURNAL ARTICLE

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

