Cyclic disulfide model of the major antigenic site of serotype-C foot-and-mouth disease virus. Synthetic, conformational and immunochemical studies.
A cyclic disulfide peptide representing antigenic site A of foot-and-mouth disease virus (FMDV) strain C-S8c1 (residues 134 to 155 of viral protein 1 (VP1) with Tyr136 and Arg153 replaced by cystine; TTCTASARGDLAHLTTTHACHL) was synthesized by solid phase methods. Formation of the cyclic disulfide was carried out by air oxidation of the fully deprotected and reduced bis-cysteine precursor, under high dilution conditions. The identity of the cyclic peptide was confirmed by both physical and enzymatic methods. A conformational study of the cyclic peptide and of its linear parent structure (YTASARGDLAHLTTTHARHLP, residues 136-156 of VP1 of FMDV C-S8c1) by circular dichroism in the presence of a structure-inducing solvent showed the cyclic disulfide analog to adopt lower levels of alpha-helix than its linear counterpart. In competitive ELISA assays both peptides reacted with similar affinity against a representative panel of neutralizing monoclonal antibodies directed towards antigenic site A. Thus, a high inherent flexibility of this loop may preclude a conformational restriction strong enough to alter recognition by anti-virus antibodies.
Camarero
J A
JA
Department of Organic Chemistry, University of Barcelona, Spain.
Andreu
D
D
Cairó
J J
JJ
Mateu
M G
MG
Domingo
E
E
Giralt
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005537:Aphthovirus / Q000737:chemistry* / Q000276:immunology; D002942:Circular Dichroism; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D012703:Serotyping; D014764:Viral Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D004220:Disulfides; D000939:Epitopes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D014764:Viral Proteins