Palladium Mediated Cleavage of Thiazolidine Backbone Modified Proteins in Live Cells.

Abstract

Chemical protein synthesis and biorthogonal modification chemistries allow production of unique proteins for a range of biological studies. Bond forming reactions for site-selective protein labeling are commonly used in these endeavors. Selective bond cleavage reactions, however, are much less explored and still pose a great challenge. In addition, most of studies with modified proteins prepared by total synthesis or semisynthetically have been applied mainly for in vitro experiments with very limited extension to live cells. Here, we report an approach for studying uniquely modified proteins containing a traceless cell delivery unit and palladium-based cleavable element for chemical activation activation and monitoring the effect of these proteins in live cells. We demonstrated this approach in the synthesis of caged ubiquitin-aldehyde, which was decaged for the inhibition of deubiquitinases in live cells.