Search

We report the stepwise transformation of a linear peptide epitope recognized by the anti-transforming growth factor alpha monoclonal antibody Tab2 into peptomers and finally into peptoid analogs. The key experiment in this study is the substitution analysis in which each position of the peptide is exchanged by a set of different peptoid building blocks resulting in a peptidomimetic array. After probing the array toward antibody binding, the best binding peptomer spots were selected and subjected to a successive transformation. The best peptoid found in this study has a K(D) of 200 nM when binding to Tab2, which is only 8-fold higher than the starting peptide. Moreover, this approach permits to ask directly questions about the transformation of peptide lead structures into non-peptidic compounds in the context of protein recognition.