Biological activities of natural and engineered cyclotides, a novel molecular scaffold for peptide-based therapeutics.
Biological activities of natural and engineered cyclotides, a novel molecular scaffold for peptide-based therapeutics.
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DOI：
10.2174/1874467211003030153
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发表时间：
2010-11
影响因子：
2.7
通讯作者：
Camarero JA
中科院分区：
文献类型：
--
作者：
Garcia AE;Camarero JA
环肽是一个不断增长的大家族的植物来源的主链环化多肽（130个氨基酸长），共享一个二硫键稳定的核心，其特征在于一个不寻常的打结结构。它们独特的环状骨架拓扑结构和三个二硫键的打结排列使它们与其他类似大小的肽相比对热，化学和酶降解非常稳定。目前，已经确定了100多个不同环肽序列的特征，预计在未来几年内，这一数字将急剧增加。考虑到它们的稳定性、生物活性和穿过细胞膜的能力，环肽类化合物可以被利用来开发具有高成功潜力的新的基于肽的药物。环肽支架可以使用分子进化来工程化或进化，以抑制与癌症和其他人类疾病有关的蛋白质-蛋白质相互作用，或设计新的抗微生物剂。本综述报告的生物多样性和治疗潜力的天然和工程环肽。
Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (≈30 amino acids long) that share a disulfide-stabilized core characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently more than 100 sequences of different cyclotides have been characterized and the number is expected to increase dramatically in the coming years. Considering their stability, biological activities and ability to cross the cell membrane, cyclotides can be exploited to develop new peptide-based drugs with high potential for success. The cyclotide scaffold can be engineered or evolved using molecular evolution to inhibit protein-protein interactions implicated in cancer and other human diseases, or design new antimicrobial. The present review reports the biological diversity and therapeutic potential of natural and engineered cyclotides.