Document 0525
 DOCN  M9650525
 TI    Extension of the polarity-dependent switch phenomenon of the gp120
       binding domain as a target for antiviral chemotherapy.
 DT    9605
 AU    Graf von Stosch A; Kinzel V; Reed J; Department of Pathochemistry,
       German Cancer Research Center,; Heidelberg, Germany.
 SO    Biochemistry. 1996 Jan 16;35(2):411-7. Unique Identifier : AIDSLINE
       MED/96140213
 AB    A 15-residue fragment within the major continuous domain of gp120 from
       HIV-1 that can bind independently to the CD4 receptor has been shown to
       have the property of behaving as a solvent polarity-dependent
       conformational switch. The switch behavior (cooperative transition from
       beta-sheet to helical conformation as a function of solvent polarity),
       which is conserved among strains with the widest sequence variability
       possible, appears to be a prerequisite for the CD4-binding ability. A
       number of switch inhibitors have been identified that destroy the
       conformational switch in the 15-residue fragment and concurrently its
       ability to bind to CD4-expressing cells. It can now be shown that the
       switch behavior and its inhibition by substances with certain shared
       structural characteristics are not restricted to the 15-residue
       subfragment, but are reflected by the behavior of the entire 44-residue
       binding domain. Further, substances active as switch inhibitors have an
       immediate effect on the conformation of the 44-residue fragment in
       aqueous buffer whereas inactive substances do not. The predictive value
       of this as a screening method is demonstrated in testing a number of new
       potential switch inhibitory compounds.
 DE    Amino Acid Sequence  Antigens, CD4/METABOLISM  Antiviral
       Agents/*PHARMACOLOGY  Binding Sites  Circular Dichroism  Drug
       Screening/METHODS  Human  HIV Envelope Protein gp120/CHEMISTRY/*DRUG
       EFFECTS/GENETICS  HIV-1/CHEMISTRY/*DRUG EFFECTS/GENETICS  In Vitro
       Molecular Sequence Data  Molecular Structure  Nuclear Magnetic Resonance
       Peptide Fragments/CHEMISTRY/DRUG EFFECTS/GENETICS  Protein Conformation
       Solvents  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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