Oligo(N‐methylalanine) as a Peptide‐Based Molecular Scaffold with a Minimal Structure and High Density of Functionalizable Sites
Oligo(N‐methylalanine) as a Peptide‐Based Molecular Scaffold with a Minimal Structure and High Density of Functionalizable Sites
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寡聚（N-甲基丙氨酸）作为基于肽的分子支架，具有最小的结构和高密度的功能位点
DOI：
10.1002/anie.202200119
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Sando Shinsuke
中科院分区：
文献类型：
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作者：
Yokomine Marin;Morimoto Jumpei;Fukuda Yasuhiro;Shiratori Yota;Kuroda Daisuke;Ueda Takumi;Takeuchi Koh;Tsumoto Kouhei;Sando Shinsuke
在水中具有纳米尺寸和限定形状的可官能化的合成分子可用作分子支架以模拟生物大分子的功能并开发用于操纵生物大分子的化学工具。在本文中，我们提出寡聚（N-甲基丙氨酸）（oligo-NMA）作为具有最小结构和高密度可官能化位点的基于肽的分子支架。Oligo-NMA在水中形成了一个确定的形状，没有氢键网络或环约束，这使得分子能够作为一个具有最小原子组成的支架。此外，可以容易地在寡NMA的氮和α-碳上引入官能团。计算和NMR光谱分析表明，oligo-NMA的骨架结构在很大程度上不受官能化的影响。此外，通过蛋白质配体的设计证明了寡NMA的有用性。合成的简易性、最小的结构和高度的功能化灵活性使oligo-NMA成为化学和生物学应用的有用支架。
Functionalizable synthetic molecules with nanometer sizes and defined shapes in water are useful as molecular scaffolds to mimic the functions of biomacromolecules and develop chemical tools for manipulating biomacromolecules. Herein, we propose oligo(N‐methylalanine) (oligo‐NMA) as a peptide‐based molecular scaffold with a minimal structure and a high density of functionalizable sites. Oligo‐NMA forms a defined shape in water without hydrogen‐bonding networks or ring constraints, which enables the molecule to act as a scaffold with minimal atomic composition. Furthermore, functional groups can be readily introduced on the nitrogens and α‐carbons of oligo‐NMA. Computational and NMR spectroscopic analysis suggested that the backbone structure of oligo‐NMA is not largely affected by functionalization. Moreover, the usefulness of oligo‐NMA was demonstrated by the design of protein ligands. The ease of synthesis, minimal structure, and high functionalization flexibility makes oligo‐NMA a useful scaffold for chemical and biological applications.