Oncode Institute and Dept. Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands; Global Research Technologies, Novo Nordisk Research Park, Måløv, Denmark.
Oncode Institute and Dept. Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Semin Cell Dev Biol. 2022 Dec;132:74-85. doi: 10.1016/j.semcdb.2021.11.025. Epub 2021 Dec 24.
Protein ubiquitination is a key post-translational modification in regulating many fundamental cellular processes and dysregulation of these processes can give rise to a vast array of diseases. Unravelling the molecular mechanisms of ubiquitination hence is an important area in current ubiquitin research with as aim to understand this enigmatic process. The complexity of ubiquitin (Ub) signaling arises from the large variety of Ub conjugates, where Ub is attached to other Ub proteins, Ub-like proteins, and protein substrates. The chemical preparation of such Ub conjugates in high homogeneity and in adequate amounts contributes greatly to the deciphering of Ub signaling. The strength of these chemically synthesized conjugates lies in the chemo-selectivity in which they can be created that are sometimes difficult to obtain using biochemical methodology. In this review, we will discuss the progress in the chemical protein synthesis of state-of-the-art Ub and Ub-like chemical probes, their unique concepts and related discoveries in the ubiquitin field.
蛋白质泛素化是调节许多基本细胞过程的关键翻译后修饰，这些过程的失调会导致大量疾病的发生。因此，揭示泛素化的分子机制是当前泛素研究的一个重要领域，旨在理解这一神秘过程。泛素（Ub）信号的复杂性源于大量的 Ub 缀合物，其中 Ub 附着在其他 Ub 蛋白、Ub 样蛋白和蛋白质底物上。这些 Ub 缀合物的化学制备具有高度的同质性和足够的数量，对揭示 Ub 信号具有重要意义。这些化学合成缀合物的优势在于它们的化学选择性，可以创建有时难以通过生化方法获得的缀合物。在这篇综述中，我们将讨论化学蛋白质合成最新 Ub 和 Ub 样化学探针的进展，以及它们在泛素领域的独特概念和相关发现。
