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Rhodium(II) Metallopeptide Catalyst Design Enables Fine Control in Selective Functionalization of Natural SH3 Domains
Author(s) -
Vohidov Farrukh,
Coughlin Jane M.,
Ball Zachary T.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201411745
Subject(s) - catalysis , covalent bond , chemistry , combinatorial chemistry , rhodium , nanotechnology , residue (chemistry) , biochemistry , materials science , organic chemistry
Chemically modified proteins are increasingly important for use in fundamental biophysical studies, chemical biology, therapeutic protein development, and biomaterials. However, chemical methods typically produce heterogeneous labeling and cannot approach the exquisite selectivity of enzymatic reactions. While bioengineered methods are sometimes an option, selective reactions of natural proteins remain an unsolved problem. Here we show that rhodium(II) metallopeptides combine molecular recognition with promiscuous catalytic activity to allow covalent decoration of natural SH3 domains, depending on choice of catalyst but independent of the specific residue present. A metallopeptide catalyst succeeds in modifying a single SH3‐containing kinase at endogenous concentrations in prostate cancer (PC‐3) cell lysate.