Li Yilong, Bi Tao, Camarero Julio A
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA; Department of Chemistry, University of Southern California, Los Angeles, CA 90033, USA.
Adv Bot Res. 2015;76:271-303. doi: 10.1016/bs.abr.2015.08.006.
Cyclotides are fascinating naturally occurring micro-proteins (≈30 residues long) present in several plant families and display various biological properties such as protease inhibitory, anti-microbial, insecticidal, cytotoxic, anti-HIV and hormone-like activities. Cyclotides share a unique head-to-tail circular knotted topology of three disulfide bridges, with one disulfide penetrating through a macrocycle formed by the two other disulfides and interconnecting peptide backbones, forming what is called a cystine knot topology. This cyclic cystine knot (CCK) framework gives the cyclotides exceptional rigidity, resistance to thermal and chemical denaturation, and enzymatic stability against degradation. Interestingly, cyclotides have been shown to be orally bioavailable, and other cyclotides have been shown to cross the cell membranes. Moreover, recent reports have also shown that engineered cyclotides can be efficiently used to target extracellular and intracellular protein-protein interactions, therefore making cyclotides ideal tools for drug development to selectively target protein-protein interactions. In this work we will review all the available methods for production of these interesting proteins using chemical or biological methods.
环肽是存在于多个植物科中的一类引人入胜的天然微蛋白（约30个残基长），具有多种生物学特性，如蛋白酶抑制、抗菌、杀虫、细胞毒性、抗HIV及激素样活性。环肽具有独特的由三个二硫键构成的头对尾环状纽结拓扑结构，其中一个二硫键穿过由另外两个二硫键形成的大环并连接肽主链，形成所谓的胱氨酸结拓扑结构。这种环状胱氨酸结（CCK）框架赋予环肽非凡的刚性、抗热和化学变性能力以及抗酶解稳定性。有趣的是，环肽已被证明具有口服生物利用性，其他环肽也已被证明能穿过细胞膜。此外，最近的报道还表明，工程化环肽可有效用于靶向细胞外和细胞内的蛋白质-蛋白质相互作用，因此使环肽成为药物开发中选择性靶向蛋白质-蛋白质相互作用的理想工具。在这项工作中，我们将综述所有利用化学或生物学方法生产这些有趣蛋白质的可用方法。
