Using the Cyclotide Scaffold for Targeting Biomolecular Interactions in Drug Development

This review provides an overview of the properties of cyclotides and their potential for developing novel peptide-based therapeutics. The selective disruption of protein–protein interactions remains challenging, as the interacting surfaces are relatively large and flat. However, highly constrained polypeptide-based molecular frameworks with cell-permeability properties, such as the cyclotide scaffold, have shown great promise for targeting those biomolecular interactions. The use of molecular techniques, such as epitope grafting and molecular evolution employing the cyclotide scaffold, has shown to be highly effective for selecting bioactive cyclotides.