Ubiquitination plays a crucial role in controlling various biological processes such as translation, DNA repair and immune response. Protein degradation for example, is one of the main processes which is controlled by the ubiquitin system and has significant implications on human health. In order to investigate these processes and the roles played by different ubiquitination patterns on biological systems, homogeneously ubiquitinated proteins are needed. Notably, these conjugates that are made enzymatically in cells cannot be easily obtained in large amounts and high homogeneity by employing such strategies. Therefore, chemical and semisynthetic approaches have emerged to prepare different ubiquitinated proteins. In this review, we will present the key synthetic strategies and their applications for the preparation of various ubiquitinated proteins. Furthermore, the use of these precious conjugates in different biochemical and functional studies will be highlighted.
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