A rationally designed synthetic mimic of the discontinuous CD4-binding site of HIV-1 gp120

Helmholtz Centre for Infection Research, Braunschweig, Germany.
Journal of Receptor and Signal Transduction Research (Impact Factor: 2.28). 02/2006; 26(5-6):453-60. DOI: 10.1080/10799890600923179
Source: PubMed


Synthetic mimetics of the CD4-binding site of HIV-1 gp120 are promising candidates for HIV-1 entry inhibition, as well as immunogen candidates for the elicitation of virus-neutralizing antibodies. On the basis of the crystal structure of gp120 in complex with CD4, we have used a recently introduced strategy for the generation of structurally diverse scaffolds to design and synthesize a scaffolded peptide, in which three fragments, making up the sequentially discontinuous binding site of gp120 for CD4, are presented in a nonlinear and discontinuous fashion through a molecular scoffold, which restrains conformational flexibility. The affinities of this molecule to CD4, as well as to the broadly neutralizing antibody mAb b12, whose epitope overlaps the CD4-binding site of gp120, were determined in competitive binding assays.

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