Synthesis and characterization of photoactivatable doxycycline analogues bearing two-photon-sensitive photoremovable groups suitable for light-induced gene expression

• Verfasst von: Goegan, Bastien [VerfasserIn]
• Verfasst von: Terzi, Firat [VerfasserIn]
• Verfasst von: Cambridge, Sidney [VerfasserIn]
• Titel: Synthesis and characterization of photoactivatable doxycycline analogues bearing two-photon-sensitive photoremovable groups suitable for light-induced gene expression
• Verf.angabe: Bastien Goegan, Firat Terzi, Frédéric Bolze, Sidney Cambridge, and Alexandre Specht
• E-Jahr: 2018
• Jahr: 17 January 2018
• Umfang: 8 S.
• Fussnoten: Gesehen am 08.05.2019
• Titel Quelle: Enthalten in: ChemBioChem
• Ort Quelle: Weinheim : Wiley-VCH, 2000
• Jahr Quelle: 2018
• Band/Heft Quelle: 19(2018), 12, Seite 1341-1348
• ISSN Quelle: 1439-7633
• DOI: doi:10.1002/cbic.201700628
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: gene expression
• Sach-SW: optopharmacology
• Sach-SW: photolysis
• Sach-SW: TetOn system
• Sach-SW: two-photon uncaging
• K10plus-PPN: 166496892X

Abstract

We report the synthesis and photolytic properties of caged 9-aminodoxycycline derivatives modified with 2-4′-bis-[2-(2methoxyethoxy)ethyl]-4-nitrobiphenyl-3-ylprop-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.