Document 0156
 DOCN  M9490156
 TI    Heparin specifically inhibits binding of V3 loop antibodies to HIV-1
       gp120, an effect potentiated by CD4 binding.
 DT    9411
 AU    Harrop HA; Coombe DR; Rider CC; Department of Biochemistry, Royal
       Holloway, University of London,; Egham, Surrey, UK.
 SO    AIDS. 1994 Feb;8(2):183-92. Unique Identifier : AIDSLINE MED/94318201
 AB    OBJECTIVE: To investigate the binding of the sulphated polysaccharides,
       dextran sulphate and heparin, to CD4 and gp120 in order to examine the
       anti-HIV mechanisms of these compounds. DESIGN: In order to study the
       molecular mechanisms involved, the binding of sulphated polysaccharides
       to recombinant (r) sCD4 and gp120 was investigated in solid-phase
       binding studies that employed various monoclonal antibodies directed
       against known epitopes on these proteins, including the V3 loop of
       gp120. METHODS: The ability of sulphated polysaccharides to inhibit both
       the binding of gp120 to CD4 and the binding of the monoclonal antibodies
       was investigated by enzyme-linked immunosorbent assays. RESULTS: It was
       demonstrated that dextran sulphate inhibits gp120-sCD4 binding at
       concentrations of 100 micrograms/ml, whereas heparin has no effect.
       Heparin does, however, block the binding to rgp120 of monoclonal
       antibodies recognizing epitopes in the V3 loop. Clinical low molecular
       weight heparin preparations are as active as unfractionated heparin in
       this regard. Pre-incubation of gp120 with excess sCD4 increases the
       potency of heparin in blocking the binding of V3 loop monoclonals
       severalfold. CONCLUSIONS: The modes of action of heparin and dextran
       sulphate differ. Dextran sulphate both inhibits CD4-gp120 binding and
       binds to the V3 loop of gp120. However, heparin is more selective and
       appears to function only by interfering with events involving the V3
       loop that occur prior to HIV fusion with the plasma membrane.
 DE    Antibodies, Monoclonal/*IMMUNOLOGY/METABOLISM  Antibody Specificity
       Antigen-Antibody Reactions/*DRUG EFFECTS  Antigens, CD4/*METABOLISM
       Comparative Study  Dextran Sulfate/PHARMACOLOGY  Enoxaparin/PHARMACOLOGY
       Enzyme-Linked Immunosorbent Assay  Heparin/*PHARMACOLOGY  Human  HIV
       Antibodies/*IMMUNOLOGY/METABOLISM  HIV Envelope Protein
       gp120/*IMMUNOLOGY/METABOLISM  HIV-1/*IMMUNOLOGY  Membrane Fusion
       Peptide Fragments/*IMMUNOLOGY/METABOLISM  Protein Binding/DRUG EFFECTS
       Recombinant Proteins/IMMUNOLOGY/METABOLISM  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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