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1996-02-26
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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).