       Document 1022
 DOCN  M9621022
 TI    Antivirals that target the amino-terminal domain of HIV type 1
       glycoprotein 41.
 DT    9602
 AU    Gordon LM; Waring AJ; Curtain CC; Kirkpatrick A; Leung C; Faull K;
       Mobley PW; Department of Pediatrics, Drew University-King Medical;
       Center/UCLA 90059, USA.
 SO    AIDS Res Hum Retroviruses. 1995 Jun;11(6):677-86. Unique Identifier :
       AIDSLINE MED/96078228
 AB    Functional and structural studies were made to assess whether a class of
       antiviral agents targets the N-terminal domain of the glycoprotein
       41,000 (gp41) of human immunodeficiency virus type 1 (HIV-1). Previous
       experiments have shown that the amino-terminal peptide (FP-I; 23 amino
       acids, residues 519-541) of HIV-1 gp41 is cytolytic to both human
       erythrocytes (non-CD4+ cells) and Hut-78 cells (CD4+ lymphocytes).
       Accordingly, FP-I-induced hemolysis may be used as a surrogate assay for
       evaluating the role of the N-terminal gp41 domain in HIV-cell
       interactions. Here, we studied the blocking of FP-I-induced lysis of
       erythrocytes by the following anti-HIV agents: (1) IgG [i.e.,
       anti-(518-541) IgG] raised to an immunoconjugate of Arg-FP-I, (2)
       apolipoprotein A-1 (apo A-1) and a peptide based on apo A-1, (3) dextran
       sulfate, (4) gp41 peptide (residues 637-666), and (5) anionic human
       serum albumins. Dose-response curves indicated that their relative
       potency in inhibiting FP-I-induced hemolysis was approximately
       correlated with their previously reported anti-HIV activity. Electron
       spin resonance (ESR) studies showed that FP-I spin labeled at the
       N-terminal alanine binds to anti-(518-541) IgG, dextran sulfate, and
       anionic albumins. The high in vitro antiviral activity and low
       cytotoxicity of these agents suggest that blocking membrane-FP-I
       interactions offers a novel approach for AIDS therapy or prophylaxis.
 DE    Amino Acid Sequence  Antibodies, Viral  Antiviral Agents/*PHARMACOLOGY
       Apolipoprotein A-I/PHARMACOLOGY  Dextran Sulfate/PHARMACOLOGY
       Erythrocyte Membrane/METABOLISM  Erythrocytes  Hemolysis  Human  HIV
       Envelope Protein gp41/CHEMISTRY/*DRUG EFFECTS/IMMUNOLOGY/
       METABOLISM/PHARMACOLOGY  HIV-1/*DRUG EFFECTS  IgG/PHARMACOLOGY
       Immunoconjugates  Molecular Sequence Data  Peptide
       Fragments/CHEMISTRY/*DRUG EFFECTS/IMMUNOLOGY/METABOLISM/  PHARMACOLOGY
       Serum Albumin/PHARMACOLOGY  Spin Labels  Support, Non-U.S. Gov't
       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).

