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Chemical synthesis and biosynthesis of the cyclotide family of circular proteins
Author(s) -
Gunasekera Sunithi,
Daly Norelle L.,
Anderson Marilyn A.,
Craik David J.
Publication year - 2006
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540600889532
Subject(s) - cyclic peptide , violaceae , computational biology , biology , structural motif , chemistry , biochemistry , combinatorial chemistry , peptide , botany
Abstract Cyclotides are a recently discovered class of proteins that have a characteristic head‐to‐tail cyclized backbone stabilized by a knotted arrangement of three disulfide bonds. They are exceptionally resistant to chemical, enzymatic and thermal treatments because of their unique structural scaffold. Cyclotides have a range of bio‐activities, including uterotonic, anti‐HIV, anti‐bacterial and cytotoxic activity but their insecticidal properties suggest that their natural physiological role is in plant defense. They are genetically encoded as linear precursors and subsequently processed to produce mature cyclic peptides but the mechanism by which this occurs remains unknown. Currently most cyclotides are obtained via direct extraction from plants in the Rubiaceae and Violaceae families. To facilitate the screening of cyclotides for structure‐activity studies and to exploit them in drug design or agricultural applications a convenient route for the synthesis of cyclotides is vital. In this review the current chemical, recombinant and biosynthetic routes to the production of cyclotides are discussed.iubmb Life, 58: 515‐524, 2006