title: Chemistry and biology of cyclotides: circular plant peptides outside the box.
abstract: Cyclotides stand out as the largest family of circular proteins of plant origin hitherto known, with more than 280 sequences isolated at peptide level and many more predicted from gene sequences. Their unusual stability resulting from the signature cyclic cystine knot (CCK) motif has triggered a broad interest in these molecules for potential therapeutic and agricultural applications. Since the time of the first cyclotide discovery, our laboratory in Uppsala has been engaged in cyclotide discovery as well as the development of protocols to isolate and characterize these seamless peptides. We have also developed methods to chemically synthesize cyclotides by Fmoc-SPPS, which are useful in protein grafting applications. In this review, experience in cyclotide research over two decades and the recent literature related to their structures, synthesis, and folding as well the recent proof-of-concept findings on their use as "epitope" stabilizing scaffolds are summarized.
authors: Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , Biomedical Centre, Box 574, SE-751 23 Uppsala, Sweden.
authors: Robert
authors: R
authors: Burman
authors: Sunithi
authors: S
authors: Gunasekera
authors: Adam A
authors: AA
authors: Strömstedt
authors: Ulf
authors: U
authors: Göransson
mesh_terms: D000595:Amino Acid Sequence; D047169:Cyclotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D047168:Cystine Knot Motifs; D008958:Models, Molecular; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D047169:Cyclotides