HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by HOWIE, S. E. M. Articles by HARRISON, D. J. Search for Related Content PubMed PubMed Citation Articles by HOWIE, S. E. M. Articles by HARRISON, D. J.

A functional, discontinuous HIV-1 gp120 C3/C4 domain-derived, branched, synthetic peptide that binds to CD4 and inhibits MIP-1 chemokine binding

Department of

^a Pathology,

^b Centre for Protein Technology, and

^c Centre for HIV Research, University of Edinburgh, U.K.

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-1. 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-1 chemokine binding.

¹ Correspondence: Department of Pathology, Edinburgh University Medical School, Teviot Place, Edinburgh EH8 9AG, U.K. E-mail: s.e.m.howie{at}ed.ac.uk

Key Words: antibody • macrophage • PBMC • monoclonal antibody • CDR2 region

This article has been cited by other articles:

				T. J. Hewson, J. J. Logie, P. Simmonds, and S. E. M. Howie A CCR5-Dependent Novel Mechanism for Type 1 HIV gp120 Induced Loss of Macrophage Cell Surface CD4 J. Immunol., April 15, 2001; 166(8): 4835 - 4842. [Abstract] [Full Text] [PDF]

				S. HOWIE, R. RAMAGE, and T. HEWSON Innate Immune System Damage in Human Immunodeficiency Virus Type 1 Infection . Implications for Acquired Immunity and Vaccine Design Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S141 - 145. [Abstract] [Full Text] [PDF]