Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany.
Institute of Biological and Chemical Systems-Functional Molecular Systems, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany.
Chem Rev. 2020 May 27;120(10):4301-4354. doi: 10.1021/acs.chemrev.9b00665. Epub 2020 May 1.
While the Staudinger reaction has first been described a hundred years ago in 1919, the ligation reaction became one of the most important and efficient bioconjugation techniques in the 1990s and this century. It holds the crucial characteristics for bioorthogonal chemistry: biocompatibility, selectivity, and a rapid and high-yielding turnover for a wide variety of applications. In the past years, it has been used especially in chemical biology for peptide/protein synthesis, posttranslational modifications, and DNA labeling. Furthermore, it can be used for cell-surface engineering, development of microarrays, and drug delivery systems. However, it is also possible to use the reaction in synthetic chemistry for general formation of amide bonds. In this review, the three major types, traceless and nontraceless Staudinger Ligation as well as the Staudinger phosphite reaction, are described in detail. We will further illustrate each reaction mechanism and describe characteristic substrates, intermediates, and products. In addition, not only its advantages but also stereochemical aspects, scope, and limitations, in particular side reactions, are discussed. Finally, the method is compared to other bioorthogonal labeling methods.
尽管 Staudinger 反应早在 1919 年就已被首次描述，但连接反应在 20 世纪 90 年代及本世纪成为最重要和最有效的生物偶联技术之一。它具有生物正交化学的关键特征：生物相容性、选择性以及广泛应用的快速高产转化率。在过去的几年中，它尤其在化学生物学中被用于肽/蛋白质合成、翻译后修饰和 DNA 标记。此外，它可用于细胞表面工程、微阵列的开发和药物输送系统。然而，该反应也可用于合成化学中一般酰胺键的形成。在这篇综述中，详细描述了三种主要类型的无痕和非无痕 Staudinger 连接以及 Staudinger 亚膦酸盐反应。我们将进一步说明每种反应机制，并描述特征性的底物、中间体和产物。此外，不仅讨论了该方法的优点，还讨论了立体化学方面、范围和限制，特别是副反应。最后，将该方法与其他生物正交标记方法进行了比较。
