Rational dissection of binding surfaces for mimicking of discontinuous antigenic sites.
Peptide-based approaches to mimicking protein interactive regions have relied mainly on linear peptides; however, most binding sites are discontinuous and thus not easily reproducible by a linear sequence. Any attempt to replicate those sites by chemical means must not only integrate all residues involved in the recognition but also provide structural organization to native-like levels. Here we describe a surface mimic approach to the reconstruction of such complex molecular architectures, using as a model a discontinuous antigenic site of foot-and-mouth disease virus that is defined by residues belonging to three different capsid proteins. Our surface mimics are synthetic cyclic peptides, designed in silico, capable of binding antibodies directed to this site, and with demonstrated functional capabilities as vaccines in guinea pigs. Further, by saturation transfer difference NMR, we have determined several antibody binding residues on these peptides.
Villén
Judit
J
Department of Experimental and Health Sciences, Pompeu Fabra University, Dr Aiguader 80, 08003 Barcelona, Spain.
Rodríguez-Mias
Ricard A
RA
Núñez
José I
JI
Giralt
Ernest
E
Sobrino
Francisco
F
Andreu
David
D
D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D018716:Molecular Mimicry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D012680:Sensitivity and Specificity
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D000939:Epitopes; D010456:Peptides, Cyclic