Poth Aaron G, Chan Lai Y, Craik David J
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Biopolymers. 2013 Sep;100(5):480-91. doi: 10.1002/bip.22284.
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.
环肽是一类天然存在的、来自植物的主链环化大环小蛋白，具有分子内三对缠结的二硫键。它们的结构特征使环肽在高温或存在蛋白水解酶的情况下具有非凡的抗降解稳定性。迄今为止已测序的250多种天然环肽体现了其半胱氨酸内环序列的可塑性，这种对序列变异的耐受性以及它们多样的生物活性，支撑了环胱氨酸结基序作为有价值的药物设计支架和蛋白质工程研究工具的适用性。在此，我们综述了环肽在稳定肽表位方面的应用及相关蛋白质工程研究的最新文献。还描述了该领域未来可能的发展方向。
