Semi-synthesis of Ubiquitin-propargylamide for identifying deubiquitinase targeting inhibitors

Abstract

Ubiquitin-propargylamide (Ub-PA) is one of the most widely used activity-based probe to measure the activity of deubiquitinases (DUBs) and help validate DUBs targeting inhibitors. However, current synthetic route of Ub-PA is cumbersome. In this work, we report a novel semi-synthetic strategy to prepare Ub-PA in large-scale. Biochemical assays prove that semi-synthetic Ub-PA is an effective probe in identifying DUBs targeting inhibitors.