Chemical and biomimetic total syntheses of natural and engineered MCoTI cyclotides.
Chemical and biomimetic total syntheses of natural and engineered MCoTI cyclotides.
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DOI：
10.1039/b801667d
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发表时间：
2008-04
影响因子：
3.2
通讯作者：
P. Thongyoo;N. Roqué-Rosell;R. Leatherbarrow;Edward W. Tate
中科院分区：
文献类型：
--
作者：
P. Thongyoo;N. Roqué-Rosell;R. Leatherbarrow;Edward W. Tate
天然存在的环状胱氨酸结微蛋白胰蛋白酶抑制剂MCoTI-I和MCoTI-II已经使用thia-zip天然化学连接和具有通过固定化蛋白酶的化学酶促环化的仿生策略合成。已经产生了在P1位置含有一系列取代的工程化类似物，这些取代将特异性重定向到替代蛋白酶靶标，同时保留优异至中等的亲和力。此外，我们报告了MCoTI类似物，它是口蹄疫病毒（FMDV）3C蛋白酶的选择性低microM抑制剂，这是首次报道的基于肽的这种重要病毒酶的抑制剂。
The naturally-occurring cyclic cystine-knot microprotein trypsin inhibitors MCoTI-I and MCoTI-II have been synthesised using both thia-zip native chemical ligation and a biomimetic strategy featuring chemoenzymatic cyclisation by an immobilised protease. Engineered analogues have been produced containing a range of substitutions at the P1 position that redirect specificity towards alternative protease targets whilst retaining excellent to moderate affinity. Furthermore, we report an MCoTI analogue that is a selective low-microM inhibitor of foot-and-mouth-disease virus (FMDV) 3C protease, the first reported peptide-based inhibitor of this important viral enzyme.