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Engineering bromodomains with a photoactive amino acid by engaging 'Privileged' tRNA synthetases
Shana Wagner1, Babu Sudhamalla, Philip Mannes
1Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA. kai27@pitt.edu.
Abstract:
Site-specific placement of unnatural amino acids, particularly those responsive to light, offers an elegant approach to control protein function and capture their fleeting 'interactome'. Herein, we have resurrected 4-(trifluoromethyldiazirinyl)-phenylalanine, an underutilized photo-crosslinker, by introducing several key features including easy synthetic access, site-specific incorporation by 'privileged' synthetases and superior crosslinking efficiency, to develop photo-crosslinkable bromodomains suitable for 'interactome' profiling.
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