Dynamic Amino Acid Side-Chains Grafting on Folded Peptide Backbone

An efficient strategy for the synthesis of large libraries of conformationnally defined peptides is reported, using dynamic combinatorial chemistry as a tool to graft amino acid side chains on a well-ordered 3D peptide backbone. Combining rationnally designed scaffolds with combinatorial side chains selection represents an alternative method to access peptide libraries for structures that are not genetically encodable. This method would allow a breakthrough for the discovery of protein mimetic for unconventional targets for which little is known.