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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).
-
-