Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences , University of Copenhagen , Universitetsparken 2 , DK-2100 Copenhagen , Denmark.
J Org Chem. 2019 Apr 5;84(7):3762-3779. doi: 10.1021/acs.joc.9b00218. Epub 2019 Mar 19.
Peptidomimetic foldamers adopting well-defined three-dimensional structures while being stable toward proteolysis are of interest in biomedical research, chemical biology, and biomimetic materials science. Despite their backbone flexibility, β-peptoids containing N-( S)-1-(1-naphthyl)ethyl ( Ns1npe) side chains can fold into unique triangular prism-shaped helices. We report herein the successful introduction of amino groups onto robustly folded β-peptoid helices by construction and incorporation of novel chiral building blocks. This is the first example of an X-ray crystal structure of a linear β-peptoid containing more than one type of side chain. We thus present a unique foldamer design comprising a robustly folded core with functionalized side chains protruding perpendicular to the helical axis to provide a highly predictable display of functional groups. This work paves the way for development of β-peptoid foldamers with a desired function, such as catalytic properties or as scaffolds enabling polyvalent display.
采用明确的三维结构且对蛋白水解稳定的肽拟折叠物在生物医学研究、化学生物学和仿生材料科学中具有重要意义。尽管具有主链柔性，但含有 N-(S)-1-(1-萘基)乙基（Ns1npe）侧链的β-肽拟物可以折叠成独特的三角棱柱形螺旋。我们在此报告了通过构建和引入新型手性砌块，成功地在结构稳定的β-肽拟物螺旋上引入氨基。这是首例含有不止一种侧链的线性β-肽拟物的 X 射线晶体结构实例。因此，我们提出了一种独特的折叠物设计，包括一个结构稳定的核心和功能化的侧链，这些侧链垂直于螺旋轴突出，从而提供了高度可预测的官能团展示。这项工作为具有所需功能（如催化性质或作为允许多价展示的支架）的β-肽拟折叠物的开发铺平了道路。
