Phosphine-Activated Lysine Analogues for Fast Chemical Control of Protein Subcellular Localization and Protein SUMOylation.

Phosphine-Activated Lysine Analogues for Fast Chemical Control of Protein Subcellular Localization and Protein SUMOylation.
Chembiochem. 2019 Oct 30;:
Authors: Wesalo JS, Luo J, Morihiro K, Liu J, Deiters A
Abstract
The Staudinger reduction and its variants have exceptional compatibility with live cells but can be limited by slow kinetics. Herein we report new small-molecule triggers that turn on proteins through a Staudinger reduction/self-immolation cascade with substantially improved kinetics and yields. We achieved this through site-specific incorporation of a new set of azidobenzyloxycarbonyl lysine derivatives in mammalian cells. This approach allowed us to activate proteins by adding a nontoxic, bioorthogonal phosphine trigger. We applied this methodology to control a post-translational modification (SUMOylation) in live cells, using native modification machinery. This work significantly improves the rate, yield, and tunability of the Staudinger reduction-based activation, paving the way for its application in other proteins and organisms.
PMID: 31664790 [PubMed - as supplied by publisher]

Source: Chembiochem - October 29, 2019 Category: Biochemistry Authors: Wesalo JS, Luo J, Morihiro K, Liu J, Deiters A Tags: Chembiochem Source Type: research