Abstract
Cyclotides are fascinating microproteins (≈30-40 residues long) with a unique head-to-tail cyclized backbone, stabilized by three disulfide bonds forming a cystine knot. This unique topology makes them exceptionally stable to chemical, thermal and biological degradation compared to other peptides of similar size. Cyclotides have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot, able to cross cellular membranes and modulate intracellular protein-protein interactions both in vitro and in vivo. These properties make them ideal scaffolds for many biotechnological applications. This article provides and overview of the properties of cyclotides and their applications as molecular imaging agents and peptide-based therapeutics.