Chemical and biological production of cyclotides.
Chemical and biological production of cyclotides.
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DOI：
10.1016/bs.abr.2015.08.006
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发表时间：
2015
影响因子：
--
通讯作者：
Camarero JA
中科院分区：
文献类型：
--
作者：
Li Y;Bi T;Camarero JA
环肽类化合物是一类天然存在的小分子蛋白质（约30个残基），广泛存在于多种植物中，具有蛋白酶抑制、抗菌、杀虫、细胞毒、抗HIV和类病毒等多种生物学活性。环肽具有独特的三个二硫键的头对尾环状打结拓扑结构，其中一个二硫键穿透由另外两个二硫键和互连肽骨架形成的大环，形成所谓的胱氨酸结拓扑结构。这种环状胱氨酸结（CCK）框架赋予环肽特殊的刚性、耐热性和化学变性性以及抗降解的酶稳定性。有趣的是，环肽已被证明是口服生物可利用的，其他环肽已被证明可以穿过细胞膜。此外，最近的报道还表明，工程化的环肽可以有效地用于靶向细胞外和细胞内蛋白质-蛋白质相互作用，因此使环肽成为药物开发的理想工具，以选择性地靶向蛋白质-蛋白质相互作用。在这项工作中，我们将审查所有可用的方法生产这些有趣的蛋白质，使用化学或生物学方法。
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.