Giant Macrolactams Based on β-Sheet Peptides
Giant Macrolactams Based on β-Sheet Peptides
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DOI：
10.1021/jo102598n
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发表时间：
2011-05-06
影响因子：
3.6
通讯作者：
Nowick, James S.
中科院分区：
文献类型：
--
作者：
Cheng, Pin-Nan;Nowick, James S.
本文报道了利用天然氨基酸、三肽β链模拟物Hao和β转角模拟物δ-连接的鸟氨酸合成水溶性54-、78-和102-元环大环内酰胺。这些巨型大环化合物是通过合成相应的保护线性肽，然后进行液相环化和脱保护而有效制备的。通过常规的基于Fmoc的固相肽合成，在2-氯三苯甲基氯树脂上合成受保护的线性肽前体。大环化通常使用HCTU和N，N-二异丙基乙胺在DMF中在约20 ° C下进行。0.5 mM浓度。在HPLC纯化和冻干后，以13-45%的总产率分离大环化合物。1D、2D TOCSY和2D ROESY（1）H NMR。对54-和78-元环大环内酰胺的研究证实，这些化合物在水溶液中折叠形成β-折叠结构。
This paper reports the use of natural amino acids, the tripeptide beta-strand mimic Hao, and the beta-turn mimic delta-linked ornithine to generate water-soluble 54-, 78-, and 102-membered-ring macrolactams. These giant macrocycles were efficiently prepared by synthesis of the corresponding protected linear peptides, followed by solution-phase cyclization and deprotection. The protected linear peptide precursors were synthesized on 2-chlorotrityl chloride resin by conventional Fmoc-based solid-phase peptide synthesis. Macrocyclization was typically performed using HCTU and N,N-diisopropylethylamine in DMF at ca. 0.5 mM concentration. The macrocycles were isolated in 13-45% overall yield after HPLC purification and lyophilization. 1D, 2D TOCSY, and 2D ROESY (1)H NMR. studies of the 54- and 78-membered-ring macrolactams establish that these compounds fold to form beta-sheet structures in aqueous solutions.