The synthesis of biomimetic helical secondary structures is sought after for the construction of innovative nanomaterials and applications in medicinal chemistry such as the development of protein-protein interaction modulators. Peptoids, a sequence-defined family of oligomers, enable a peptidomimetic strategy, especially considering the easily accessible monomer diversity and peptoid helical folding propensity. However, cis-trans isomerization of the backbone tertiary amides may impair the peptoid's adoption of stable secondary structures, notably the all-cis polyproline I-like helical conformation. Here, we show that cis-inducing NtBu achiral monomers strategically positioned within chiral sequences may reinforce the degree of peptoid helicity, although with a reduced content of chiral side chains. The design principles presented here will undoubtedly help achieve more conformationally stable helical peptoids with desired functions.

中文翻译：

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通过酰胺顺式诱导NtBu单体的序列位点特异性定位来增强类肽螺旋度。

寻求仿生螺旋二级结构的合成，用于构建创新的纳米材料，并将其应用于药物化学，例如蛋白质-蛋白质相互作用调节剂的开发。类肽是序列定义的寡聚物家族，可实现拟肽策略，尤其是考虑到易于获得的单体多样性和类肽螺旋折叠倾向。但是，主链叔酰胺的顺反异构化可能会损害类肽对稳定二级结构的采用，尤其是全顺式脯氨酸I样螺旋构象。在这里，我们显示策略性地定位在手性序列内的顺式诱导NtBu非手性单体可能会增强类肽螺旋度，尽管手性侧链的含量降低。