A functional, discontinuous HIV-1 gp120 C3/C4 domain-derived, branched, synthetic peptide that binds to CD4 and inhibits MIP-1alpha chemokine binding
| Autor: | Marilyn Moore, Graham Cotton, Donald Innes, Tim J. Hewson, Mark L. Fernandes, David J. Harrison, Sarah E. M. Howie, Robert Ramage, Ian Heslop |
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| Rok vydání: | 1999 |
| Předmět: |
Chemokine
medicine.drug_class Protein Conformation CCR3 Molecular Sequence Data Fluorescent Antibody Technique Peptide Enzyme-Linked Immunosorbent Assay HIV Infections HIV Envelope Protein gp120 Monoclonal antibody Biochemistry Chemokine receptor Mice Genetics medicine Animals Humans Amino Acid Sequence Binding site Chemokine CCL4 Molecular Biology Cells Cultured Chemokine CCL3 Antiserum chemistry.chemical_classification Mice Inbred BALB C Binding Sites biology Chemistry Macrophages virus diseases Macrophage Inflammatory Proteins Peptide Fragments Chemokine binding CD4 Antigens biology.protein HIV-1 Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 13(3) |
| ISSN: | 0892-6638 |
| Popis: | This paper describes a branched synthetic peptide [3.7] that incorporates sequence discontinuous residues of HIV-1 gp120 constant regions. The approach was to bring together residues of gp120 known to interact with human cell membranes such that the peptide could fold to mimic the native molecule. The peptide incorporates elements of both the conserved CD4 and CCR5 binding sites. The 3.7 peptide, which cannot be produced by conventional genetic engineering methods, is recognized by antiserum raised to native gp120. The peptide also binds to CD4 and competitively inhibits binding of QS4120 an antibody directed against the CDR2 region of CD4. When preincubated with the CD4+ve MM6 macrophage cell line, which expresses mRNA for the CCR3 and CCR5 chemokine receptors, both 3.7 and gp120 inhibit binding of the chemokine MIP-1alpha. The peptide also inhibits infection of primary macrophages by M-tropic HIV-1. Thus, 3.7 is a prototype candidate peptide for a vaccine against HIV-1 and represents a novel approach to the rational design of peptides that can mimic complex sequence discontinuous ligand binding sites of clinically relevant proteins. |
| Databáze: | OpenAIRE |
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