Structure-based design of peptides that recognize the CD4 binding domain of HIV-1 gp120.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Structure-based design of peptides that recognize the CD4 binding domain of HIV-1 gp120.

AIDS. 1998 Aug 20;12(12):1413-8. Unique Identifier : AIDSLINE MED/98394544
Fontenot JD; Tan X; Phillips DM; Population Council, Center for Biomedical Research, New York, New; York 10021, USA.

Abstract: DESIGN: Envelope protein-specific antiviral peptides, called mucibodies, that can specifically recognize and bind to the surface unit protein gp120 of HIV-1 were designed. The initial mucibody binding target was the V3 loop of HIV-1 gp120. Here, the gp120-CD4 binding domain was chosen as the site of mucibody binding. The CD4 binding domain of gp120 is known to be a conformational epitope and is involved in the earliest events of viral entry into many cells. METHODS: The design of the mucibody antivirals was based on previous observations that antibody complementarity determining regions (CDR) are generally similar to the repeating loops or knob structures found in the 20-residue tandem repeat domain of human mucin MUC1. The heavy chain CDR3 from the bacteriophage display antibody b12 was used to construct two mucibodies, b12-CDR1 and b12-26. RESULTS: Peptides corresponding to three tandem repeats were shown to bind directly to the CD4 binding domain of HIV-1 gp120 in a solid-phase enzyme-linked immunosorbent assay. These mucibody peptides also disrupted the gp120-CD4 interaction in a solution-phase inhibition assay. Finally, mucibodies neutralized primary and laboratory macrophage-tropic isolates of HIV-1. CONCLUSIONS: There is a potential for medical use of these peptides as topical vaginal microbicides in preventing HIV-1 transmission during sexual contact. These results also suggest that multivalent, non-immunogenic binding proteins of virtually any specificity could be constructed for use in therapeutic applications involving infectious diseases and immune system dysfunction.

Keywords: JOURNAL ARTICLE Anti-HIV Agents/CHEMISTRY/METABOLISM Antigens, CD4/*METABOLISM Binding Sites Enzyme-Linked Immunosorbent Assay Human HIV Antibodies/*CHEMISTRY HIV Antigens/CHEMISTRY HIV Envelope Protein gp120/*METABOLISM HIV Infections/PREVENTION & CONTROL *HIV-1 Mucins/CHEMISTRY Neutralization Tests Peptides/CHEMISTRY/*CHEMICAL SYNTHESIS/*METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Tandem Repeat Sequences
990130
A9911041

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