1 research outputs found
Design of an Activity-Based Probe for Human Neutrophil Elastase: Implementation of the Lossen Rearrangement To Induce Förster Resonance Energy Transfers
Human
neutrophil elastase is an important regulator of the immune
response and plays a role in host defense mechanisms and further physiological
processes. The uncontrolled activity of this serine protease may cause
severe tissue alterations and impair inflammatory states. The design
of an activity-based probe for human neutrophil elastase reported
herein relies on a sulfonyloxyphthalimide moiety as a new type of
warhead that is linker-connected to a coumarin fluorophore. The inhibitory
potency of the activity-based probe was assessed against several serine
and cysteine proteases, and the selectivity for human neutrophil elastase
(<i>K</i><sub>i</sub> = 6.85 nM) was determined. The adequate
fluorescent tag of the probe allowed for the in-gel fluorescence detection
of human neutrophil elastase in the low nanomolar range. The coumarin
moiety and the anthranilic acid function of the probe, produced in
the course of a Lossen rearrangement, were part of two different Förster
resonance energy transfers