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Cyclotides as grafting frameworks for protein engineering and drug design applications
Author(s) -
Poth Aaron G.,
Chan Lai Y.,
Craik David J.
Publication year - 2013
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22284
Subject(s) - chemistry , protein engineering , scaffold , computational biology , disulfide bond , intramolecular force , protein design , combinatorial chemistry , biochemistry , protein structure , stereochemistry , enzyme , biology , computer science , database
Cyclotides are a family of naturally occurring backbone‐cyclized macrocyclic mini‐proteins from plants that have a knotted trio of intramolecular disulfide bonds. Their structural features imbue cyclotides with extraordinary stability against degradation at elevated temperatures or in the presence of proteolytic enzymes. The plasticity of their intracysteine loop sequences is exemplified by the more than 250 natural cyclotides sequenced to date, and this tolerance to sequence variation, along with their diverse bioactivities, underpins the suitability of the cyclic cystine knot motif as a valuable drug design scaffold and research tool for protein engineering studies. Here, we review the recent literature on applications of cyclotides for the stabilization of peptide epitopes and related protein engineering studies. Possible future directions in this field are also described. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 480–491, 2013.