Wang Shixue, Tao Yue, Wang Jianqun, Tao Youhua, Wang Xianhong
Key Laboratory of Polymer Ecomaterials , Changchun Institute of Applied Chemistry , Chinese Academy of Sciences , Renmin Street 5625 , Changchun 130022 , People's Republic of China . Email:
University of Chinese Academy of Sciences , Beijing 100039 , People's Republic of China.
Chem Sci. 2018 Nov 22;10(5):1531-1538. doi: 10.1039/c8sc03415j. eCollection 2019 Feb 7.
Designing artificial macromolecules with absolute sequence order is still a long-term challenge in polymer chemistry as opposed to natural biopolymers with perfectly defined sequences like proteins and DNA. Herein, we combined amino acid building blocks and iterative Ugi reactions for the design and synthesis of sequence-defined peptoids. The highly efficient strategy provided excellent yields and enables multigram-scale synthesis of perfectly defined peptoids. This new strategy furnishes the broad structural diversity of side chains, as well as backbones. Importantly, the overall hydrophobicity and lower critical solution temperature (LCST) behaviours of these precisely defined peptoids can be logically altered by variation of the sequence. By following the same Ugi chemistry, these peptoids are also conjugated to DNA in a simple way, facilitating the development of novel therapeutics.
与具有如蛋白质和DNA那样完美定义序列的天然生物聚合物不同，设计具有绝对序列顺序的人工大分子仍然是聚合物化学领域的一项长期挑战。在此，我们将氨基酸构建模块与迭代Ugi反应相结合，用于序列定义类肽的设计与合成。这种高效策略提供了优异的产率，并能够进行克级规模的完美定义类肽的合成。这一新策略提供了侧链以及主链的广泛结构多样性。重要的是，通过改变序列，可以合理地改变这些精确定义类肽的整体疏水性和低临界溶液温度（LCST）行为。通过遵循相同的Ugi化学方法，这些类肽还能以简单的方式与DNA结合，促进新型治疗药物的开发。
