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Palladium‐Mediated Cleavage of Proteins with Thiazolidine‐Modified Backbone in Live Cells
Author(s) -
Mann Guy,
Satish Gandhesiri,
Meledin Roman,
Vamisetti Ganga B.,
Brik Ashraf
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201906545
Subject(s) - chemistry , semisynthesis , thiazolidine , palladium , cleavage (geology) , in vitro , chemical synthesis , protein biosynthesis , aldehyde , ubiquitin , combinatorial chemistry , biochemistry , biology , catalysis , paleontology , fracture (geology) , gene
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 either total synthesis or semisynthesis have been applied mainly for in vitro experiments with very limited extension to live cells. Reported here is an approach for studying uniquely modified proteins containing a traceless cell delivery unit and palladium‐based cleavable element for chemical activation, and monitoring the effect of these proteins in live cells. This approach is demonstrated for the synthesis of a caged ubiquitin‐aldehyde, which was decaged for the inhibition of deubiquitinases in live cells.