The Revised Structure of the Cyclic Octapeptide Surugamide A
The Revised Structure of the Cyclic Octapeptide Surugamide A
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DOI：
10.1248/cpb.c19-00002
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发表时间：
2019-05-01
影响因子：
1.7
通讯作者：
Wakimoto, Toshiyuki
中科院分区：
文献类型：
--
作者：
Matsuda, Kenichi;Kuranaga, Takefumi;Wakimoto, Toshiyuki
苏糖酰胺类化合物是从海洋来源的链霉菌中分离得到的一组非核糖体多肽。苏糖酰胺A(1)及其亲缘关系密切的衍生物B-E(2-5)是含有D-氨基酸的环八肽类化合物，具有组织蛋白酶B抑制活性。D-异亮氨酸(Ile)是嵌入在1中的非蛋白性氨基酸残基，在天然多肽中不太常见，因为它的生物合成需要罕见的C-β-异构化。利用本课题组先前建立的2的合成路线，我们采用固相法合成了含有D-Ile的环状八肽1。化学合成和层析比较证实了1的结构中含有D-allo-Ile而不是D-Ile。
Surugamides are a group of non-ribosomal peptides isolated from marine-derived Streptomyces. Surugamide A (1) and its closely related derivatives, surugamides B-E (2-5), are D-amino acid containing cyclic octapeptides with cathepsin B inhibitory activity. The D-isoleucine (Ile), the nonproteinogenic amino acid residue embedded in 1, is less common in natural peptides because a rare C-beta-epimerization is required for its biosynthesis. Taking advantage of the synthetic route of 2 previously established by our group, we synthesized the cyclic octapeptide 1 containing D-Ile by solid phase peptide synthesis. The structure of 1 actually contains D-allo-Ile in place of D-Ile, which was corroborated by chemical syntheses and chromatographic comparisons.