Design of an Activity-Based Probe for Human Neutrophil Elastase: Implementation of the Lossen Rearrangement To Induce Förster Resonance Energy Transfersстатья
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Дата последнего поиска статьи во внешних источниках: 10 августа 2018 г.
Аннотация: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 (Ki = 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.