Cyclic disulfide model of the major antigenic site of serotype-C foot-and-mouth disease virus: Synthetic, conformational and immunochemical studies

• Published in: FEBS letters 1993-08, Vol.328 (1), p.159-164
• Main Authors: Camarero, Julio A., Andreu, David, Cairó, Jordi J., Mateu, Mauricio G., Domingo, Esteban, Giralt, Ernest
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antigenic peptide; Aphthovirus - chemistry; Aphthovirus - immunology; Biological and medical sciences; Circular Dichroism; Conformational restriction; Disulfides - chemical synthesis; Disulfides - chemistry; Disulfides - immunology; Enzyme-Linked Immunosorbent Assay; Epitopes - chemistry; Fundamental and applied biological sciences. Psychology; Mice; Microbiology; Models, Molecular; Molecular Sequence Data; Monoclonal antibody; Morphology, structure, chemical composition, physicochemical properties; Peptide Fragments; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Peptides, Cyclic - immunology; Protein Conformation; Serotyping; Solid phase peptide syntesis; Viral Proteins - chemical synthesis; Viral Proteins - chemistry; Viral Proteins - immunology; Virology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(93)80985-4

A cyclic disulfide peptide representing antigenic site A of foot-and-mouth-disease virus (FMDV) strain C-S8cl (residues 134 to 155 of viral protein l (VP1) with Tyr 136 and Arg 153 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-S8cl) by circular dichroism in the presence of a structure-inducing solvent showed the cyclic disulfide analog to adopt lower levels of α-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.