LAUSR

We report the synthesis and photolytic properties of caged 9‐aminodoxycycline derivatives modified with 2‐{4′‐bis‐[2‐(2methoxyethoxy)ethyl]‐4‐nitrobiphenyl‐3‐yl}prop‐1‐oxy (EANBP) and PEG7‐ylated (7‐diethylamino‐2‐oxo‐2H‐chromen‐4‐yl)methyl (PEG7‐DEACM) groups. 9‐Aminodoxycycline is a tetracycline analogue capable of activating transcription through the inducible TetOn transgene expression system and can be regioselectively coupled to two‐photon‐sensitive photo‐removable protecting groups by carbamoylation. The EANBP‐based caged 9‐aminodoxycycline showed complex photochemical reactions but did release 10 % of 9‐aminodoxycycline. However, 9‐(PEG7‐DEACMamino)doxycycline exhibited excellent photolysis efficiency at 405 nm with quantitative release of 9‐aminodoxycycline and a 0.21 uncaging quantum yield. Thanks to the good two‐photon sensitivity of the DEACM chromophore, 9‐aminodoxycycline release by two‐photon photolysis is possible, with calculated action cross‐sections of up to 4.0 GM at 740 nm. Therefore, 9‐(PEG7‐DEACMamino)doxycycline represents a very attractive tool for the development of a light‐induced gene expression method in living cells.