A rationally designed synthetic mimic of the discontinuous CD4-binding site of HIV-1 gp120.
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.
Franke
Raimo
R
Helmholtz Centre for Infection Research, Braunschweig, Germany.
Hirsch
Tatjana
T
Eichler
Jutta
J
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000378:metabolism*; D015195:Drug Design; D000939:Epitopes / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D018716:Molecular Mimicry; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments