Protein receptors are known normally to bind to their target ligands via epitopes, which constitute a small proportion of the total protein molecule. For maximum binding or interaction, the structure of the epitope needs to be maintained in a rigid conformation in order to form a binding site containing all the necessary components of the epitope in close proximity. Attempts to produce an analogous peptide constructed solely of the amino acids comprising the binding site often fail because these peptides do not possess the same biological activity as the protein receptor. This is attributed to the peptide having a different conformation in free solution from that of the entire protein receptor. In addition, where the binding site of a protein is constructed of oligo-peptides from different, non-contiguous parts of a protein chain, mixing isolated oligopeptides in free solution does not result in reconstitution of the active binding site.
Being constrained to use such large proteins to present binding-site epitopes gives rise to several problems in development of new receptor-specific therapeutic strategies. One problem is that such large proteins can readily evoke an immune response. A second problem is that long peptide chains are susceptible to attack by endopeptidases, such as those in the lumen of the gut. Finally, these large proteins can be costly to manufacture, purify and maintain in stable form.