ICS Prize of Excellence 2019
A decade of chemistry with ubiquitin signaling

The modification of proteins by ubiquitin (Ub), i.e., ubiquitination, mediates a variety of cellular processes such as DNA repair, and viral infections. Understanding the molecular mechanism of ubiquitination in these processes is the basis for unraveling its precise role in health and disease. However, the inherent complexity of Ub signaling due to the high atomic complexity of Ub conjugates, where Ub is attached to other Ub molecules and to protein substrates in various forms, imposes a major challenge for these studies. In this regard, the enzymatic approaches employed for the preparation of important Ub conjugates have severe limitations to deliver them in high homogeneity and in adequate amounts for the desired study. In this talk I will present our efforts during the past decade in developing novel chemical approaches to prepare various Ub conjugates with precise control over the atomic structure. I will present examples on how these conjugates significantly have contributed to deciphering Ub signaling at the molecular level and the use of unique synthetic conjugates in drug discovery efforts.