Different strategies for the peptidomimetic design of an active compound

Protein-protein interactions are essential in all biological processes. Small peptides have been shown to be useful to induce or displace those interactions. However, their therapeutic use is limited because they are easily degraded in the body and therefore have to be injected intravenously.

Aminoacids are obvious intermediates for the design of libraries since they have at least two reactive centres. Historically, combinatorial synthesis was designed to produce libraries of millions of peptides to assay all the combinations of natural and non-natural aminoacids. New structures were identified but they had the same drawbacks than the natural ligands.

Parallel synthesis introduced the concept of peptidomimetics, small protein-like chains designed to mimic a peptide. Several strategies were designed to stabilize the sequence: peptide cyclisation, isosteric replacement, aminoacid replacement, beta-turn mimics, ... Our peptidomimetic libraries are offering new core structures for the identification of potent peptide-like inhibitors.