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We report the first molecular system that is responsive to both a bio-specific and a bio-orthogonal stimulus. This dual activation process was applied to the design of a biothiol-specific FRET-based fluorescent probe that could be turned-on via an original concept of quencher bleaching.

Bio-specific and bio-orthogonal chemistries to switch-off the quencher of a FRET-based fluorescent probe: application to living-cell biothiol imaging