Constrained peptide libraries as a tool for finding mimotopes

The monoclonal antibody (mAb) KAA8 recognizes the peptide angiotensin II (AII). The KAA8 mAb was biopanned using two phage-displayed peptide libraries, one unconstrained, the other constrained by a disulfide bond. After several cycles of biopanning, both libraries showed enrichment for phage that bind KAA8. Phage isolated from the unconstrained library contain a consensus sequence that matches the sequence of AII. A consensus sequence was also identified from the constrained library that does not resemble the AII sequence, and represents a mimotope of AII. We have also demonstrated that monovalent phage display can be used to discriminate between modest and high-affinity binding peptides.