Ubiquitination, a key and extensive posttranslational modification of proteins, has profound effects on a variety of physiological and pathological processes. The inherent complexity of ubiquitin conjugates makes it h...Ubiquitination, a key and extensive posttranslational modification of proteins, has profound effects on a variety of physiological and pathological processes. The inherent complexity of ubiquitin conjugates makes it highly challenging to study the functional and structural mechanisms of ubiquitination. To address these challenges, accesses to sufficient poly-ubiquitin chains or ubiquitinated proteins are urgently needed. Over the last decade, synthetic protein chemists have developed several novel peptide ligation methods for the preparation of ubiquitin conjugates with precise control over the atomic structure. In this review, we summarize the recent breakthroughs and potential challenges in the chemical synthesis and semi-synthesis of ubiquitin conjugates with respect to the preparation of poly-ubiquitin-based proteins and ubiquitin-based probes.展开更多
基金supported by the National Natural Science Foundation of China (21807063, 91753120, U1732161, 81503094)the start-up grant from Qingdao University (41118010086)the China Postdoctoral Science Foundation (2016 M600524)
文摘Ubiquitination, a key and extensive posttranslational modification of proteins, has profound effects on a variety of physiological and pathological processes. The inherent complexity of ubiquitin conjugates makes it highly challenging to study the functional and structural mechanisms of ubiquitination. To address these challenges, accesses to sufficient poly-ubiquitin chains or ubiquitinated proteins are urgently needed. Over the last decade, synthetic protein chemists have developed several novel peptide ligation methods for the preparation of ubiquitin conjugates with precise control over the atomic structure. In this review, we summarize the recent breakthroughs and potential challenges in the chemical synthesis and semi-synthesis of ubiquitin conjugates with respect to the preparation of poly-ubiquitin-based proteins and ubiquitin-based probes.
