| Autor: |
Zhang, Xuekai, Lu, Gang, Sun, Meng, Mahankali, Madhu, Ma, Yanfei, Zhang, Mingming, Hua, Wangde, Hu, Yuting, Wang, Qingbing, Chen, Jinghuo, He, Gang, Qi, Xiangbing, Shen, Weijun, Liu, Peng, Chen, Gong |
| Zdroj: |
Nature Chemistry; May 2018, Vol. 10 Issue: 5 p540-548, 9p |
| Abstrakt: |
New methods capable of effecting cyclization, and forming novel three-dimensional structures while maintaining favourable physicochemical properties are needed to facilitate the development of cyclic peptide-based drugs that can engage challenging biological targets, such as protein–protein interactions. Here, we report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalysed intramolecular C(sp3)–H arylation reactions. Easily accessible linear peptide precursors of simple and versatile design can be selectively cyclized at the side chains of either aromatic or modified non-aromatic amino acid units to form various cyclophane-braced peptide cycles. This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures. Preliminary cell proliferation screening of the pilot library revealed a potent lead compound with selective cytotoxicity toward proliferative Myc-dependent cancer cell lines. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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