Cyclotides represent a new class of natural plant compounds, which could be considered ideal "template" molecules for drug design. Their structure is characterized by a circular cystine-knot motif, comprising an amino acid chain stabilized by three conserved disulfide bonds in a knotted arrangement, and a head-to-tail cyclized peptide backbone. Our laboratories initially demonstrated their activity to modulate immune cell signaling. Following nearly a decade of extensive research, we are now aware that cyclotide-based peptides provide an outstanding opportunity to develop novel drugs for autoimmune disorders, especially multiple sclerosis. Here we review and demonstrate the potential of cyclotide-derived peptide therapeutics on their way from preclinical studies to clinical trials as promising therapeutics in immunopharmacological applications.
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