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A functional, discontinuous HIV‐1 gp120 C3/C4 domain‐derived, branched, synthetic peptide that binds to CD4 and inhibits MIP‐1α chemokine binding
Author(s) -
Howie Sarah E. M.,
Fernandes Mark L.,
Heslop Ian,
Hewson Tim J.,
Cotton Graham J.,
Moore Marilyn J.,
Innes Donald,
Ramage Robert,
Harrison David J.
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.3.503
Subject(s) - peptide , chemokine receptor , gp41 , chemokine , peptide sequence , c c chemokine receptor type 6 , microbiology and biotechnology , receptor , cxcr4 , biology , binding site , consensus sequence , chemistry , biochemistry , antibody , epitope , gene , immunology
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‐1α. 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.—Howie, S. E. M., Fernandes, M. L., Heslop, I., Hewson, T. J., Cotton, G. J., Moore, M. J., Innes, D., Ramage, R., Harrison, D. J. A discontinuous HIV‐1 gp120 C3/C4 domain‐derived, branched, synthetic peptide that binds to CD4 and inhibits MIP‐1α chemokine binding. FASEB J. 13, 503–511 (1999)