In this section
@article{Walter:2021:10.1021/jacs.0c12864,
author = {Walter, E and Ge, Y and Mason, J and Boyle, J and Long, N},
doi = {10.1021/jacs.0c12864},
journal = {Journal of the American Chemical Society},
pages = {6460--6469},
title = {A coumarin-porphyrin FRET break-apart probe for heme oxygenase-1},
url = {http://dx.doi.org/10.1021/jacs.0c12864},
volume = {143},
year = {2021}
}
TY - JOUR
AB - Heme oxygenase-1 (HO-1) is a vital enzyme in humans that primarily regulates free heme concentrations. The overexpression of HO-1 is commonly associated with cardiovascular and neurodegenerative diseases including atherosclerosis and ischemic stroke. Currently, there are no known chemical probes to detect HO-1 activity, limiting its potential as an early diagnostic/prognostic marker in these serious diseases. Reported here are the design, synthesis, and photophysical and biological characterization of a coumarin–porphyrin FRET break-apart probe to detect HO-1 activity, Fe–L1. We designed Fe–L1 to “break-apart” upon HO-1-catalyzed porphyrin degradation, perturbing the efficient FRET mechanism from a coumarin donor to a porphyrin acceptor fluorophore. Analysis of HO-1 activity using Escherichia coli lysates overexpressing hHO-1 found that a 6-fold increase in emission intensity at 383 nm was observed following incubation with NADPH. The identities of the degradation products following catabolism were confirmed by MALDI-MS and LC–MS, showing that porphyrin catabolism was regioselective at the α-position. Finally, through the analysis of Fe–L2, we have shown that close structural analogues of heme are required to maintain HO-1 activity. It is anticipated that this work will act as a foundation to design and develop new probes for HO-1 activity in the future, moving toward applications of live fluorescent imaging.
AU - Walter,E
AU - Ge,Y
AU - Mason,J
AU - Boyle,J
AU - Long,N
DO - 10.1021/jacs.0c12864
EP - 6469
PY - 2021///
SN - 0002-7863
SP - 6460
TI - A coumarin-porphyrin FRET break-apart probe for heme oxygenase-1
T2 - Journal of the American Chemical Society
UR - http://dx.doi.org/10.1021/jacs.0c12864
UR - http://hdl.handle.net/10044/1/89198
VL - 143
ER -
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