Target-Activated Coumarin Phototriggers Specifically Switch on Fluorescence and Photocleavage upon Bonding to Thiol-Bearing Protein

A new concept in which only the molecular target, such as a thiol-bearing protein, can activate the phototrigger has been demonstrated. Such target-activatable phototriggers comprise three parts: a 7-aminocoumarin phototrigger, an electron acceptor (maleimide) that efficiently quenches the coumarin excited state, and a caged leaving group attached to the coumarin. In the absence of mercaptans, photoinduced electron transfer between coumarin and maleimide effectively blocks both the fluorescence and photocleavage pathways. Thiol-bearing molecules, however, readily annihilate the electron acceptor and thus restore the phototrigger for photorelease of the caged cargo (e.g., biotin). Unlike traditional phototriggers, functional-group-activated phototriggers allow easy handling under ambient light, report specific bonding to the target, and enable photocleavage capability selectively at the binding site in situ, thus effectively positioning the photoreleased cargo at the target. Meanwhile, the unique feature of thiol-specific activation of the fluorescence and photocleavage make our new phototrigger a universal tool that can be used to identify accurately protein cysteine S-nitrosylation, a physiologically important posttranslational modification

Styryl Conjugated Coumarin Caged Alcohol: Efficient Photorelease by Either One-Photon Long Wavelength or Two-Photon NIR Excitation

The synthesis and photorelease properties of a new phototrigger for alcohols are described. Compared to ester <b>4</b> caged by the reported [7-(diethylamino)coumarin-4-yl]methoxycarbonyl (DEACM) phototrigger, the caged ester <b>3</b> shows an efficient single-photon photolysis efficiency upon irradiation of long wavelength light (λ = 475 nm) and a stronger two-photon photolysis sensitivity with 800 nm laser light. Its promising properties and the efficient photorelease of adenosine make it very useful as a caging group for biological applications