Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia, 30322, United States.
Angew Chem Int Ed Engl. 2024 May 27;63(22):e202403215. doi: 10.1002/anie.202403215. Epub 2024 Mar 26.
Inspired by the enzyme lysyl oxidase, which selectively converts the side chain of lysine into allysine, an aldehyde-containing post-translational modification, we report herein the first chemical method for the synthesis of allysine by selective oxidation of dimethyl lysine. This approach is highly chemoselective for dimethyl lysine on proteins. We highlight the utility of this biomimetic approach for generating aldehydes in a variety of pharmaceutically active linear and cyclic peptides at a late stage for their diversification with various affinity and fluorescent tags. Notably, we utilized this approach for generating small-molecule aldehydes from the corresponding tertiary amines. We further demonstrated the potential of this approach in generating cellular models for studying allysine-associated diseases.
受酶赖氨酰氧化酶的启发，该酶选择性地将赖氨酸的侧链转化为含有醛基的翻译后修饰物——高丝氨酸内酯，我们在此报告了通过二甲赖氨酸的选择性氧化来合成高丝氨酸内酯的第一种化学方法。这种方法对蛋白质上的二甲赖氨酸具有高度的化学选择性。我们强调了这种仿生方法在各种具有生物活性的线性和环状肽的后期生成醛的用途，可用于通过各种亲和性和荧光标记物对其进行多样化。值得注意的是，我们利用该方法从相应的叔胺生成小分子醛。我们还进一步证明了该方法在生成用于研究高丝氨酸内酯相关疾病的细胞模型方面的潜力。
