1 research outputs found
Activatable Fluorescence Probe via Self-Immolative Intramolecular Cyclization for Histone Deacetylase Imaging in Live Cells and Tissues
Histone deacetylases
(HDACs) play essential roles in transcription
regulation and are valuable theranostic targets. However, there are
no activatable fluorescent probes for imaging of HDAC activity in
live cells. Here, we develop for the first time a novel activatable
two-photon fluorescence probe that enables <i>in situ</i> imaging of HDAC activity in living cells and tissues. The probe
is designed by conjugating an acetyl-lysine mimic substrate to a masked
aldehyde-containing fluorophore via a cyanoester linker. Upon deacetylation
by HDAC, the probe undergoes a rapid self-immolative intramolecular
cyclization reaction, producing a cyanohydrin intermediate that is
spontaneously rapidly decomposed into the highly fluorescent aldehyde-containing
two-photon fluorophore. The probe is shown to exhibit high sensitivity,
high specificity, and fast response for HDAC detection <i>in
vitro</i>. Imaging studies reveal that the probe is able to directly
visualize and monitor HDAC activity in living cells. Moreover, the
probe is demonstrated to have the capability of two-photon imaging
of HDAC activity in deep tissue slices up to 130 μm. This activatable
fluorescent probe affords a useful tool for evaluating HDAC activity
and screening HDAC-targeting drugs in both live cell and tissue assays