Phage displayed 6-mer mimotopes with a consensus proline absent in the minimized linear wild-type epitope

Phage displayed random 6-mer libraries were screened with a monoclonal antibody specific for a minimized linear 7-mer epitope of the measles virus hemagglutinin protein. No clone with the wild-type sequence was selected and most clones contained a sequence motif not found in the wild-type sequence. Two mimotopes (LYMPQLS, SEMPQLP) were synthesized which inhibited binding to the measles virus 95–135 times better than a wild-type peptide. Sequence comparison of proteins with known 3D-structure indicates that the epitope corresponds to an -helix, while the best mimotopes have no predicted helix propensity. The proline is thought to be required for inducing a turn necessary for mimicking part of the -helix. The higher intrinsic stability of such a mimotope may explain its improved binding and may be more suitable in immunogenicity experiments.