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Contemporary Approaches for Site‐Selective Dual Functionalization of Proteins
Author(s) -
Xu Lujuan,
Kuan Seah Ling,
Weil Tanja
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202012034
Subject(s) - surface modification , posttranslational modification , nanotechnology , computer science , folding (dsp implementation) , combinatorial chemistry , crosstalk , dual (grammatical number) , computational biology , chemistry , toolbox , materials science , biochemistry , biology , engineering , art , programming language , literature , electronic engineering , electrical engineering , enzyme
Site‐selective protein functionalization serves as an invaluable tool for investigating protein structures and functions in complicated cellular environments and accomplishing semi‐synthetic protein conjugates such as traceable therapeutics with improved features. Dual functionalization of proteins allows the incorporation of two different types of functionalities at distinct location(s), which greatly expands the features of native proteins. The attachment and crosstalk of a fluorescence donor and an acceptor dye provides fundamental insights into the folding and structural changes of proteins upon ligand binding in their native cellular environments. Moreover, the combination of drug molecules with different modes of action, imaging agents or stabilizing polymers provides new avenues to design precision protein therapeutics in a reproducible and well‐characterizable fashion. This review aims to give a timely overview of the recent advancements and a future perspective of this relatively new research area. First, the chemical toolbox for dual functionalization of proteins is discussed and compared. The strengths and limitations of each strategy are summarized in order to enable readers to select the most appropriate method for their envisaged applications. Thereafter, representative applications of these dual‐modified protein bioconjugates benefiting from the synergistic/additive properties of the two synthetic moieties are highlighted.