Supramolecular catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While significant strides have been made in the supramolecular host-promoted synthesis of small molecules, applications of this reactivity to chemoselective and site-selective modification of complex biomolecules remain virtually unexplored. We report here a supramolecular system where coencapsulation of pyridine-borane with a variety of molecules including enones, ketones, aldehydes, oximes, hydrazones, and imines effects efficient reductions under basic aqueous conditions. Upon subjecting unprotected lysine to the host-mediated reductive amination conditions, we observed excellent ε-selectivity, indicating that differential guest binding within the same molecule is possible without sacrificing reactivity. Inspired by the post-translational modification of complex biomolecules by enzymatic systems, we then applied this supramolecular reaction to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin.
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Article Synopsis
- Site-selective chemical modifications of proteins are becoming essential in fields like biology, materials science, and medicine, allowing for precise changes that enhance protein functions.
- This method offers advantages over traditional protein expression techniques by enabling the addition of a variety of functional groups, including those not coded by genetics, leading to new protein variants with unique properties.
- The review highlights the growing focus on dual or multiple modifications due to the inadequacy of single modifications, discussing recent advancements, their benefits, challenges, and future possibilities in this emerging area.
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