Functional mimicry of a discontinuous antigenic site by a designed synthetic peptide

J. Villen, E. Borras, W.M.M. Schaaper, R.H. Meloen, M. Davila, E. Domingo, E. Giralt, D. Andreu

    Research output: Contribution to journalArticleAcademicpeer-review

    22 Citations (Scopus)

    Abstract

    Functional reproduction of the discontinuous antigenic site D of foot-and-mouth disease virus (FMDV) has been achieved by means of synthetic peptide constructions that integrate each of the three protein loops that define the antigenic site into a single molecule. The site D mimics were designed on the basis of the X-ray structure of FMDV type C-S8c1 with the aid of molecular dynamics, so that the five residues assumed to be involved in antigenic recognition are located on the same face of the molecule, exposed to solvent and defining a set of native-like distances and angles. The designed site D mimics are disulfide-linked heterodimers that consist of a larger unit containing VP2(71-84), followed by a polyproline module and by VP3(52-62), and a smaller unit corresponding to VP1(188-194) (VP=viral protein). Guinea pig antisera to the peptides recognized the viral particle and competed with site D-specific monoclonal antibodies, while inoculation with a simple (not covalently joined to one another) admixture of the three VP1-VP3 sequences yielded no detectable virus-specific serum conversion. Similar results have been reproduced in two bovines. Antisera to the peptides also moderately neutralize FMDV in cell cultures and partially protect guinea pigs against challenge with the virus. These results demonstrate functional mimicry of the discontinuous site D by the peptides, which are therefore obvious candidates for a multicomponent, peptide-based vaccine against FMDV
    Original languageEnglish
    Pages (from-to)175-182
    JournalChemBioChem
    Volume3
    Issue number39509
    DOIs
    Publication statusPublished - 2002

    Keywords

    • mouth-disease virus
    • monoclonal-antibodies
    • bioactive peptides
    • canine parvovirus
    • natural host
    • hiv-1 gp120
    • protection
    • vaccines
    • epitopes
    • protein

    Fingerprint Dive into the research topics of 'Functional mimicry of a discontinuous antigenic site by a designed synthetic peptide'. Together they form a unique fingerprint.

  • Cite this

    Villen, J., Borras, E., Schaaper, W. M. M., Meloen, R. H., Davila, M., Domingo, E., ... Andreu, D. (2002). Functional mimicry of a discontinuous antigenic site by a designed synthetic peptide. ChemBioChem, 3(39509), 175-182. https://doi.org/10.1002/1439-7633(20020301)3:2/3<175::AID-CBIC175>3.0.CO;2-W