Target-Activated Coumarin Phototriggers Specifically Switch on Fluorescence and Photocleavage upon Bonding to Thiol-Bearing Protein
- 6 March 2012
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 134 (11), 5052-5055
- https://doi.org/10.1021/ja300475k
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- Photoswitchable Nanoprobes Offer Unlimited Brightness in Frequency-Domain ImagingJournal of the American Chemical Society, 2011
- Recent advances in the photochemical control of protein functionTrends in Biotechnology, 2010
- Development and applications of photo-triggered theranostic agentsAdvanced Drug Delivery Reviews, 2010
- Anticancer Drug Release from a Mesoporous Silica Based Nanophotocage Regulated by Either a One- or Two-Photon ProcessJournal of the American Chemical Society, 2010
- Photoactive molecules for applications in molecular imaging and cell biologyChemical Society Reviews, 2010
- Activation of membrane-permeant caged PtdIns(3)P induces endosomal fusion in cellsNature Chemical Biology, 2010
- Illuminating the Chemistry of Life: Design, Synthesis, and Applications of “Caged” and Related Photoresponsive CompoundsACS Chemical Biology, 2009
- Caged compounds: photorelease technology for control of cellular chemistry and physiologyNature Methods, 2007
- Highly Efficient and Ultrafast Phototriggers for cAMP and cGMP by Using Long-Wavelength UV/Vis-ActivationAngewandte Chemie-International Edition, 2001
- Brominated 7-hydroxycoumarin-4-ylmethyls: Photolabile protecting groups with biologically useful cross-sections for two photon photolysisProceedings of the National Academy of Sciences of the United States of America, 1999