Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
Angew Chem Int Ed Engl. 2019 Mar 4;58(10):3143-3146. doi: 10.1002/anie.201813048. Epub 2019 Jan 25.
Proline derivatives bearing substituents at Cγ are valuable tools for biological and materials investigations. However, the stereochemistry at Cγ can produce undesired steric or stereoelectronic interactions. Here, we introduce γ-azaproline (γ-azPro), which lacks a stereogenic center at Cγ, as a pH-responsive and functionalizable proline analogue that can adapt to its environment. Conformational analyses by NMR spectroscopy and DFT calculations revealed that the imidazolidine ring of γ-azPro is flexible. Incorporation of γ-azPro into collagen model peptides (CMPs) produced pH-responsive triples helices and triple helices that can be easily functionalized.
γ-取代脯氨酸衍生物是生物和材料研究中非常有价值的工具。然而，Cγ 上的立体化学可能会产生不需要的空间或立体电子相互作用。在这里，我们引入了γ-氮杂脯氨酸（γ-azPro），它在 Cγ 处没有手性中心，是一种对 pH 敏感且可功能化的脯氨酸类似物，可以适应其环境。通过 NMR 光谱和 DFT 计算的构象分析表明，γ-氮杂脯氨酸的咪唑烷环是柔性的。将 γ-氮杂脯氨酸掺入胶原模型肽（CMP）中，可产生对 pH 敏感的三螺旋和可轻松功能化的三螺旋。
