Probing the role of proline as a recognition element in peptide antigens

The role of the imino acid S-proline in controlling local conformation in oligopeptides is a topic of much pharmacological interest. Recent work on the design and construction of synthetic vaccines, and of antagonists to peptides such as bradykinin, has revealed its importance in controlling molecular structure responsible for observed biological activity. Additional impetus to research on this structural problem has been provided by the startling discovery that cyclophilin, a protein that binds the immuno-suppressive drug cyclosporin A, can catalyse the slow isomerisation of X-Pro amide bonds in oligopeptides. We have attempted to probe the molecular mechanism by which proline exerts its conformational influence using a series of non-natural amino acid replacements in studies on the recognition of small peptides by monoclonal antibodies.